Kurzgesagt – In a Nutshell
Kurzgesagt – In a Nutshell
Embedded Files
Sources – Cisplatin
Sources – Cisplatin
We thank the following experts for their feedback and corrections:
– Prof. Michal Chovanec (https://www.youtube.com/@DrChovanec)
Comenius University, Bratislava, Slovakia
– Prof. Steven de Jong
University of Groningen, Netherlands
– Prof. Daniel Nettersheim
University Hospital of Düsseldorf, Germany
– Prof. Michael Spinella
Cancer Center at Illinois, University of Illinois Urbana-Champaign, USA
Disclaimer: This script is based on the personal experiences of our head writer and founder, Philipp Dettmer, as well as scientific knowledge of testicular cancer and cisplatin generally. Cisplatin is a chemotherapy drug used in the treatment of different cancers. It is often combined with other chemotherapy drugs, depending on the type of cancer, the patient’s medical situation etc. In this video, we focus on just cisplatin in the context of testicular cancer.
How to check your testicles:
https://www.nhs.uk/tests-and-treatments/how-to-check-your-testicles/
– In 2018 I was being treated for stage 3 B testicular cancer that had metastasized into a few lymph nodes and my lung.
Testicular cancer is categorized into stages 0 to 3 (with subcategories A, B etc.).
#American Cancer Society. Stages of Testicular Cancer. Retrieved July 2026
https://www.cancer.org/cancer/types/testicular-cancer/detection-diagnosis-staging/staging.html
Quote: “The earliest stage of testicular cancer is stage 0 (also called germ cell neoplasia in situ, or GCNIS). The other stage groupings range from I (1) through III (3). There is no stage IV (4) testicular cancer. Some stages are split further to cover more details, using capital letters (A, B, etc.).”
– Very serious business unfortunately, boys and men, check your testicles tonight.
#National Health Service – How to check your testicles. Retrieved July 2026
https://www.nhs.uk/tests-and-treatments/how-to-check-your-testicles/
Quote: “It's important to check your testicles (balls) regularly (around once a month) for symptoms of testicular cancer and other conditions.
Why you should check your testicles
Checking your testicles regularly means you can get to know what is normal for you.
This makes it easier to notice any changes that could be signs of a condition such as testicular cancer.
Men and boys should start checking their testicles from puberty onwards (usually from around the age of 12 years old). Anyone with testicles should check theirs regularly.”
– One day my doctor was about to punish my body with a fresh dose of Cisplatin. A cytotoxic hazardous chemotherapy agent. One of the absolutely worst ones.
Cisplatin is a chemotherapy drug used in the treatment of different cancers. It is often combined with other chemotherapy drugs, depending on the type of cancer, the patient’s medical situation etc. In this script, we focus on just cisplatin in the context of testicular cancer.
#National Cancer Institute. Cisplatin. Retrieved July 2026
http://cancer.gov/about-cancer/treatment/drugs/cisplatin
Quote: “Cisplatin is a type of chemotherapy drug called an alkylating agent. It contains the metal platinum, which binds to and damages the cell’s DNA, preventing it from being repaired or copied. This stops cells from dividing and causes them to die.
[...] Cisplatin is approved to be used alone or with other drugs to treat:
Bladder cancer. It is used alone in patients with advanced cancer that cannot be treated with other therapies, such as surgery or radiation therapy.
Ovarian cancer that has spread to other parts of the body. It is used with other drugs in patients who have already had surgery or radiation therapy. It is used alone in patients whose cancer has not gotten better with standard chemotherapy and who have not received previous cisplatin.
Testicular cancer that has spread to other parts of the body. It is used with other drugs in patients who have already had surgery or radiation therapy.
Cisplatin is also being studied in the treatment of other types of cancer.”
– My buddy Cisplatin came in a green, opaque two liter bag directly from the fridge.
The cisplatin solution used for chemotherapy is colorless, but it often comes in opaque, colored bags to protect it from light.
The unopened commercial bag of cisplatin is nowadays usually stored at room temperature. But the diluted infusion prepared by the pharmacy may be refrigerated before use depending on local pharmacy protocols and how long it will be stored.
#Electronic Medicines Compendium. Cisplatin 1mg/ml Injection BP. Retrieved July 2026
– The doctor connected the infusion to the central venous access in my chest, a tube that led directly to my heart.
A “central venous catheter” is a thin, flexible tube inserted into a large vein, usually in the chest or arm, that ends just above the heart. It is a standard administration technique for chemotherapy, allowing for continuous drug delivery without repeated needle sticks into smaller (e.g. arm) veins.
#MacMillan Cancer Support. Central lines. Retrieved July 2026
Quote: “A central line is a long, thin hollow tube. It is put into a vein in your chest and used to give chemotherapy and other drugs.”
– My doctor, who I trusted deeply, was terrified of a single drop of Cisplatin.
Because cisplatin attacks DNA, the solution used for injection during chemotherapy is considered a hazardous chemical and should be handled by medical personnel with appropriate caution. Possible risks of exposure include severe skin or eye irritation, severe organ damage when swallowed, and cancer/heritable genetic damage upon longer exposure.
The exact risks depend on the type of cisplatin medication used. Below we quote a representative information sheet for one type of cisplatin medication.
#Pfizer. Material Safety Data Sheet – Cisplatin. 2011
https://cdn.pfizer.com/pfizercom/products/material_safety_data/PZ01470.pdf
– Cisplatin is a heavy metal compound. A tiny molecule with a platinum atom at its center that looks like a quadcopter.
#TargetMol. Cisplatin (Synonyms: cis-Diaminodichloroplatinum, CDDP). Retrieved July 2026
– In the 1960s physicist Barnett Rosenberg wanted to see if he could manipulate living beings with electricity and learn interesting things because why not. Well it turns out electricity did nothing but instead he found something huge: The bacteria in a solution with platinum electrodes turned into spaghetti, 300 times longer – but way more important: They stopped multiplying. It turned out platinum molecules did that.
In Barnett’s experiments, the platinum electrodes were electrolyzing and releasing platinum coordination complexes, i.e. complex compounds with a platinum atom at their core, into the solution. This is what we mean by “platinum molecules”.
#National Cancer Institute. The "Accidental" Cure—Platinum-based Treatment for Cancer: The Discovery of Cisplatin. 2014
https://www.cancer.gov/research/progress/discovery/cisplatin
Quote: “In the experiment that led to the discovery of cisplatin in 1965, Barnett Rosenberg, Ph.D., was following a hunch. Dr. Rosenberg, a biophysics researcher at Michigan State University (MSU), had noticed that microscopic images of dividing cells resembled the pattern of iron shavings subjected to a magnetic field. He wondered whether this meant that an electrical field could also affect cell division, so he devised an experiment to find out.
An "accidental" discovery leads to cisplatin. Because platinum was thought to have no biological activity, Dr. Rosenberg and his colleagues put platinum electrodes into a solution containing the common laboratory bacteria E. coli and turned on the power. As soon as the current started, the bacterial cells stopped dividing, although they kept growing to up to 300 times their normal length. When the power was cut off, the bacterial cells began dividing again. It appeared that the electrical field was controlling cell division. Dr. Rosenberg later called this experiment the "accidental discovery that led eventually to cisplatin."
However, Dr. Rosenberg and his colleagues did not yet know what they had discovered. They thought they might have found a way to control cell growth with electrical currents. They spent two years trying to discover why the electrical field had such a profound effect. Finally, they realized that electricity had nothing to do with it. Cell division was being blocked not by the electric field, but by a platinum compound released from the electrodes. After another two years, Dr. Rosenberg's team identified the compound that affected cell division so dramatically. It was later named cisplatin.”
#Molecular Weights. The Biophysicist Who Accidentally Found a Cancer Drug. 2026
https://www.molecularweights.com/p/cisplatin-accidental-cancer-drug
Quote: “Rosenberg’s first interpretation was the obvious one: the electric field blocked division. He spent two years testing that hypothesis before the evidence forced him somewhere else entirely.2
It wasn’t electricity. Platinum was leaching from the electrodes into the growth medium, forming soluble coordination compounds in the ammonium chloride solution. Two more years went to identifying which platinum species was responsible.
The culprit turned out to be a molecule that inorganic chemists already knew: cis-diamminedichloroplatinum(II). Two ammonia groups and two chloride ions arranged around a central platinum atom in a flat, square geometry.1 Alfred Werner had characterized platinum complexes decades earlier. No one had thought to test them against living cells.
What made the finding stranger still: the trans isomer, identical in composition but with its chlorides on opposite sides of the platinum center, did almost nothing to bacteria. Geometry at the atomic scale separated inert from lethal.”
#In remembrance of Barnett Rosenberg. Dalton Trans. 2009
https://pubs.rsc.org/en/content/articlehtml/2009/dt/b918993a
Quote: “In 1963, Barney and his laboratory technician, Loretta Van Camp, initiated the research that led to the discovery of cisplatin. While the idea was wholly conceived by Barney, Loretta Van Camp carried out all the experimental work. Their goal was to examine the effect(s) of an electric field on dividing E. coli bacteria, the impetus apparently being two-fold: (1) to provide students with a biologically-oriented project (i.e., implement the “bio” in biophysics) and (2) to address a speculative notion held at the time that a magnetic component might be operating in mitosis. Barney addressed this notion in a talk given at the Sheraton Hotel in NY. He noted the visual similarity of the pattern characteristic of the separation of chromosomes in the telophase of mammalian cell division and that of the lines of force between the poles of a magnet. From this, he reasoned that cell division might be affected (coupled) by the magnetic component of an electrical field. As numerous accounts of the serendipitous discovery of cisplatin have reported, these investigators set up a continuous culture apparatus containing E. coli bacteria in a protein-free (Medium C) culture medium. Two platinum foil electrodes, connected to a sonic generator and immersed in the culture medium, were used to generate the electric field. Shortly after the field was generated, a key observation was made—the bacteria had undergone filamentous growth. Dr. Rosenberg knew instantly that cell division was inhibited, but not cell growth, facilitating the filaments to reach lengths of up to 300 times their normal length. Dr. Rosenberg also fully understood what the implications of this observation were.
James E. Trosko, Distinguished MSU Professor of Pediatrics and Human Development, was a graduate student at MSU working on his Ph.D. in the Biology Research Building during the time period (1961–1963) when Barney began this research. He recalls that Barney remarked to a group of biology graduate students before he started the historic bacterial experiments that “I am going to cure cancer”. Apparently, Barney had recently attended a seminar that inspired this comment. As a theoretician, Barney had no equipment of his own and had to borrow all the equipment needed to do the critical experiments. Dr. Trosko also recalls that he was present in the lab on the very day that the key discovery was made. On this day, Trosko was the first to arrive at the Biology Research Building and opened the lab door to the room where the bacterial experiment was in progress. An overpowering stench, emanating from the continuous culture apparatus (chemostat), permeated the room and building. He saw the bacterial mess which Barney later dubbed “spaghetti-like”. As Professor Trosko recalls, when Barney arrived later in the morning and saw the “spaghetti-like” filamentous growth, he exclaimed, “I've just cured cancer”. Previous accounts of the discovery of cisplatin state that Rosenberg's research was not cancer-oriented. With a witness to the key experiment, the discovery takes on a new perspective.”
#ROSENBERG, B., VAN CAMP, L. & KRIGAS, T. Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode. Nature 205, 698–699 (1965).
https://www.nature.com/articles/205698a0
Quote: “IN an investigation of the possible effects of an electric field on growth processes in bacteria, we have discovered a new and interesting effect. In E. coli, the presence of certain group VIIIb transition metal compounds in concentrations of about 1–10 parts per million of the metal in the culture medium causes an inhibition of the cell division process. The bacteria form long filaments, up to 300 times the normal length, which implies that the growth process is not markedly affected.”
#Encyclopedia Britannica. Cisplatin. Retrieved July 2026
https://www.britannica.com/science/cisplatin-drug
Quote: “In subsequent experiments Rosenberg discovered that this effect was due to the presence of cisplatin, a product formed by electrochemical oxidation of platinum electrodes immersed in a nutrient medium that contained ammonium chloride as a pH buffer.”
– At the time chemotherapy was gaining popularity as a treatment for cancer – any chemical that stopped cell division was a potential candidate.
#Gach-Janczak, K.; Drogosz-Stachowicz, J.; Janecka, A.; Wtorek, K.; Mirowski, M. Historical Perspective and Current Trends in Anticancer Drug Development. Cancers 2024
https://www.mdpi.com/2072-6694/16/10/1878
Quote: “Cancer is considered one of the leading causes of death in the 21st century. The intensive search for new anticancer drugs has been actively pursued by chemists and pharmacologists for decades, focusing either on the isolation of compounds with cytotoxic properties from plants or on screening thousands of synthetic molecules. Compounds that could potentially become candidates for new anticancer drugs must have the ability to inhibit proliferation and/or induce apoptosis in cancer cells without causing too much damage to normal cells. Some anticancer compounds were discovered by accident, others as a result of long-term research. In this review, we have presented a brief history of the development of the most important groups of anticancer drugs, pointing to the fact that they all have many side effects.”
– Rosenberg felt like he should inject cisplatin into mice with cancer to see what happened because why not. And oh boy, did things happen! While high doses turned out to be deadly to the poor rodents, on lower doses their tumors shrank, did not come back and the mice survived!
#National Cancer Institute. The "Accidental" Cure—Platinum-based Treatment for Cancer: The Discovery of Cisplatin. 2014
https://www.cancer.gov/research/progress/discovery/cisplatin
Quote: “Researchers use cisplatin to control cancer cell division and expansion. Dr. Rosenberg then wondered whether cisplatin would also block cell division in tumors. Testing it in a sarcoma mouse model, he and his colleagues found that it did indeed attack tumors. While cisplatin was highly toxic—for example, causing kidney damage when used at a high dose—the mice were able to tolerate the drug in low doses. More importantly, the tumors responded to cisplatin and shrank. Six months later, the mice remained healthy and showed no return of the tumors.”
#In remembrance of Barnett Rosenberg. Dalton Trans. 2009
https://pubs.rsc.org/en/content/articlehtml/2009/dt/b918993a
Quote: “In 1968, Barney made what he later called the “purely intuitive jump” and tested cisplatin in mice in which Sarcoma 180 solid tumor had been implanted seven days earlier. This test was a stiff challenge because instead of treating the mice on the day after the tumor was implanted (standard protocol at the time), Rosenberg and Van Camp waited until the tumor had grown to about 1 g in weight (from an initial 50 mg fragment). The results were dramatic, producing a high percentage of complete “cures”.”
#ROSENBERG, B., VANCAMP, L., TROSKO, J. et al. Platinum Compounds: a New Class of Potent Antitumour Agents. Nature 222, 385–386 (1969).
Quote: “Certain platinum compounds completely but reversibly inhibit cell division in Gram-negative rods1–4. These compounds have been tested for antitumour activity and we report some of the preliminary results. The platinum compounds inhibit sarcoma 180 and leukaemia L1210 in mice.
The most efficacious compounds tested so far are: (1) cis-Pt(IV)(NH3)3Cl2; (2) cis-Pt(II)(NH3)2Cl2; (3) Pt-(II)(NH2CH2CH2NH2)2 and (4) Pt(IV)(NH2CH2CH2NH2)Cl4. These compounds were injected intraperitoneally into mice in 0.5 ml. of saline or buffer solutions. No inoculations were given to the controls, and no positive controls were used. Sarcoma 180 tests were performed in our laboratory using ICR mice and a tumour line provided by Dr S. Poilly of the NIH. Protocols of the Cancer Chemotherapy National Service Center5 (CCNSC) were rigidly observed. The results of these tests are given in Table 1.
Because injection could, from the recorded weight losses, cause at most a T/C × 100 value of 50 per cent6 those compounds are effective in inhibiting the tumour. Some treated mice have been kept alive after treatment and have remained free from tumours for 6 months. Palpation indicates that the initial tumour transplant has disappeared. The mice appear normal and healthy. [...] Tolerance tests which are in progress show that higher doses of these compounds affect the intestinal crypt cells, causing a gelatinous appearance of the intestines in autopsies and a reduction in the size of the spleen. These effects are reversible and animals survive if injections are stopped a few days before death would have occurred.”
– Many experts were sceptical: Heavy metals are notoriously toxic and not worth the risk.
#National Cancer Institute. The "Accidental" Cure—Platinum-based Treatment for Cancer: The Discovery of Cisplatin. 2014
https://www.cancer.gov/research/progress/discovery/cisplatin
Quote: “At first, the cancer research community was skeptical about cisplatin. Heavy metals were considered poisons, and "the idea of putting a heavy metal into a person was an abomination," Dr. Rosenberg recalled.”
#MSU Libraries. Interview with Barnett Rosenberg. 2001
https://d.lib.msu.edu/otb-sohp/165
Quote: “Once we had that, we went to the Cancer Institute. I had a friend there. They invited me down to give a talk on this, and they were rather reluctant to become interested, because the idea of putting a heavy metal into a person was an abomination. “Heavy metals are poisonous. And you’re putting a poison into a person? No way.””
– But Rosenberg kept pushing and lobbying – at one point calling drug developers weekly until cisplatin was finally tested in humans.
#Blum R, Rozencweig M, Muggia F. Remembering Stephen K. Carter, MD, and His National and International Impact on Early Drug Development. 2017
Quote: “In 2003, at a New York University gathering on platinums honoring Barnett Rosenberg and his discovery of cisplatin as an anticancer drug, Steve reminisced: “Your persistence in calling me every week to ask me ‘how is my drug doing?’ certainly helped move it along our NCI pipeline.”
#MSU Libraries. Interview with Barnett Rosenberg. 2001
https://d.lib.msu.edu/otb-sohp/165
Quote: “So the idea of a whole field of chemistry now allowing us to get our foot into the field of cancer research, nobody else could do the chemistry research but the specialists in platinum chemistry. So they jumped on the wagon, and very soon we had large numbers of people very much interested in this. Other people published, and it grew and grew, and eventually the Cancer Institute tried the Neumanns [phonetic] in 1972 with success. And off we went.
In ’78, we got the patent on it, and at the same time, the FDA gave us the approval for injecting it in human beings. Out of the number of companies, there were about five companies that were interested in the license for it, Bristol-Myers at the time, now Bristol-Myers-Squibb, got the license with the best offer, and they’ve been pursuing it ever since and with a fair degree of success.”
Seeking further approval for licensing & production (post FDA approval):
#In remembrance of Barnett Rosenberg. Dalton Trans. 2009
https://pubs.rsc.org/en/content/articlehtml/2009/dt/b918993a
Quote: “Although cisplatin was approved by the Federal Drug Administration (FDA), there was considerable reluctance by pharmaceutical companies to license/market the drug despite the fact that all the initial clinical studies were underwritten by the NCI. This reluctance underscored the feeling and skepticism that pharmacologists had about the likelihood that metal complexes could have useful biological activity. In this regard, Barney visited almost every major pharmaceutical company in the world trying to interest them in licensing cisplatin. The valiant efforts of Archie Perstayko and Stanley Crooke finally convinced Bristol-Myers to license cisplatin (and later carboplatin) from MSU.”
– Cisplatin was used on a wide variety of patients with different cancer types. Not only did the heavy metal not really slow down most cancers, it kind of killed some patients.
It is quite hard to tell what the patients died from in these early/historic clinical trials. One patient was confirmed to have died from kidney damage, two additional ones were suspected to have died from kidney damage since their autopsy revealed severe kidney damage.
This 1972 study showed weak tumor effects but no reported deaths:
#Rossof, A.H., Slayton, R.E. and Perlia, C.P. (1972), Preliminary clinical experience with cis-diamminedichloroplatinum (II) (NSC 119875, CACP). Cancer, 30: 1451-1456.
Quote: “Thirty-one patients with metastatic cancer were treated with ris-diammine-dichloroplatinum (11), CACP, in dosages ranging from 7.5 to 200 mg/m'BSA per course. [...] Evidence for antitumor activity was noted in 5 of our 31 patients. Four of the five responding patients experienced moderate-to-severe toxicity. These data are summarized in Table 5 .”
This 1973 study showed weak tumor effects, and 1 patient (of 10) died from kidney problems:
#DeConti RC, Toftness BR, Lange RC, Creasey WA. Clinical and pharmacological studies with cis-diamminedichloroplatinum (II). Cancer Res. 1973 Jun;33(6):1310-5. PMID: 4515709.
https://aacrjournals.org/cancerres/article/33/6/1310/479684
Quote: “Objective evidence of antineoplastic effects could be documented in only 1 patient (Table 1). This subject (R. R.) who had acute granulocytic leukemia, experiences a fall in peripheral blast count from 25,000 to 3,000 after receiving the largest single dose used in this
study, 3.15 mg/kg. Because this response was short, a 2nd smaller dose of drug (1.20 mg/kg) was given 16 days after the initial dose. In the week that followed, he developed progressive azotemia and died with florid leukemia and sepsis. A renal biopsy revealed cortical edema, focal tubular calcification, red blood cell and hemoglobin casts, and focal tubular necrosis. Milder evidence of renal impairment was the most significant toxic manifestation of drug treatment. Transient proteinuria was seen in 4 patients. Normal pretreatment serum creatinines rose to greater than 2 mg/100 ml in 3 of 6 patients who received dosages of 1.95 mg or more per kg. Creatinine values returned to within normal limits, and cumulative effects were not noted in 3 patients who received total dosages of 3.9 to 4.8 mg/kg.”
This 1978 publication references a study from 1973, which reported autopsies of two patients (of 21) with kidney damage:
#Madias NE, Harrington JT. Platinum nephrotoxicity. Am J Med. 1978
https://www.sciencedirect.com/science/article/abs/pii/0002934378908252
Quote: “21 patients, 35 cis-DDPt(ll) courses (9 patients received more than one course) [...] Tubular necrosis in 2 autopsy patients”
– In early studies, up to 75% of patients got severe kidney damage. It’s hard to prove if that’s what killed them though, as they were already dying of cancer.
#Goldstein RS, Mayor GH. Minireview. The nephrotoxicity of cisplatin. Life Sci. 1983
https://www.sciencedirect.com/science/article/abs/pii/0024320583902990?via%3Dihub
Quote: “Early clinical trials revealed that the incidence of nephrotoxicity may range from 25-33% and 50-75% following single and multiple course therapy with cisplatin, respectively (2,14).”
#Madias NE, Harrington JT. Platinum nephrotoxicity. Am J Med. 1978
https://www.sciencedirect.com/science/article/abs/pii/0002934378908252
Quote: “Current evidence suggests that single courses of cis-DDPt (II) in the range of 2 mg/kg or 50 to 75 mg/m* body surface area will produce renal toxicity in a quarter to a third of the patients treated. A similar incidence of toxicity is expected with the regimen of 15 to 20 mg/m* body surface area administered for five days. However, toxicity after a single course of either of these two regimens is usually mild to moderate and reversible. At higher doses, nephrotoxicity appears more frequently and is more severe in nature. Moreover, the currently available evidence suggests that in a significant percentage of such cases, nephrotoxicity will be irreversible. The development of platinum nephrotoxicity also appears to depend on the cumulative effect of the cis-DDPt (II) administered as is the case with organic mercurials [1,18,20].”
Earlier study reporting kidney damage in 24-100% of treatment courses (not patients):
#Rossof, A.H., Slayton, R.E. and Perlia, C.P. (1972), Preliminary clinical experience with cis-diamminedichloroplatinum (II) (NSC 119875, CACP). Cancer, 30: 1451-1456.
Quote: “The renal injury was reversible in nearly every patient, but, as in other causes of tnbu-lar necrosis, complete recovery was riot attained in each patient, as evidenced by incom-plete recovery of the endogenous creatinine clearance in some patients. Percutaneous renal biopsies were obtained in two patients with clinical evidence of acute renal injury. In each case, there was evidence of acute tubular necrosis with tubular degeneration and intersti-tial edema. Electron microscopy performed on this tissue revealed swollen, degenerating, vacuolated mitochondria and disruption of the brush border microvilli. The details of these findings will be reported elsewhere, T h mechanism of this tubular injury is notknown, but i t is similar to that reported in rats and marmosets receiving CACP."11 Severe nephrotoxicity was seen in patients with preexisting abnormalities of the excretory ap-paratus.”
– And then an astonishing study rocked the medical world: 11 patients with advanced testicular cancer, the most common cancer among young men, received cisplatin. 6 responded somewhat, and three… went into complete remission. In more human words: they were cured. This was unheard of.
#Higby, D.J., Higby, D.J., Wallace, H.J., Jr., Albert, D.J. and Holland, J.F. (1974), Diaminodichloroplatinum: A phase I study showing responses in testicular and other tumors. Cancer, 33: 1219-1225.
Quote: “Diaminodichloroplatinum was studied in a Phase I trial. Two dose schedules were explored. In Schedule I, a maximum dose of 100 mg/M2 given once was reached, and this proved too toxic for further use. The maximum dose in Schedule II, 24 mg/M2 daily for 5 days, was also too toxic, so 20 mg/M2 per day for 5 days was the dose selected for further exploration. Responses were seen in 1 patient with anaplastic thyroid carcinoma, 1 with transitional cell carcinoma of the bladder, and 1 with breast cancer. In patients with testicular tumors, responses were seen in 9 of 11 patients. There were 3 complete regressions seen, 1 in seminoma, 1 in embryonal cell carcinoma, and 1 in male choriocarcinoma. Three partial regressions, and three cases of objective improvement were also seen in this series. These were also distributed over different tumor types. The possibility that diaminodichloroplatinum has a specific effect on tissues arising from the genitourinary anlage is suggested.”
– Until this moment, metastatic testicular cancer was super deadly, 95% of all men who got it died.
#Einhorn LH. Curing metastatic testicular cancer. Proc Natl Acad Sci U S A. 2002
https://pmc.ncbi.nlm.nih.gov/articles/PMC123692/
Quote: “Testicular cancer has become a model for a curable neoplasm. In the early 1970s, metastatic testicular cancer was associated with only 5% survival.”
– Another one made cisplatin finally bearable: A new protocol of massive overhydration – basically the patient would be flooded with liters and liters of fluid to flush the Cisplatin out of the kidneys. If you are wondering, yes, this means that you pee all day and night.
Modern protocols for cisplatin administration typically involve giving the patient several liters of saline solution. The goal is to dilute the drug and flush it out of the kidney quickly, before it can cause too much damage there.
#National Health Service. Guidelines for Cisplatin Hydration. 2023
https://www.kmcc.nhs.uk/s3/assets/cisplatin-hydration-guidelines-v4-1688558672.pdf
– The game for testicular cancer flipped.
After Higby et al. 1974 (which we mention above, the study with the 11 patients) there was another famous landmark trial: Einhorn et al. 1977, a Phase II trial. It was the next big breakthrough in using cisplatin against testicular cancer.
#LAWRENCE H. EINHORN, JOHN DONOHUE. Cis-Diamminedichloroplatinum, Vinblastine, and Bleomycin Combination Chemotherapy in Disseminated Testicular Cancer. Ann Intern Med.1977
https://www.acpjournals.org/doi/10.7326/0003-4819-87-3-293
Quote: “Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became disease-free after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6+ to 30+ months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer.”
#In remembrance of Barnett Rosenberg. Dalton Trans. 2009
https://pubs.rsc.org/en/content/articlehtml/2009/dt/b918993a
Quote: “In 1971, cisplatin entered clinical trials in the U. S. at several locations. An international platinum symposium held in Oxford in 1973 was looming as a sort of cisplatin showdown, because clinicians using cisplatin were confronted with dose-limiting kidney toxicity that they had never experienced previously with any other anticancer drug and for which no amelioration was known. This crisis nearly ended the use of cisplatin as an antitumor drug. Fortunately, the astounding results of Dr. Lawrence Einhorn and his team at Indiana University School of Medicine in treating testicular cancer, for which no known effective anticancer drug was available at the time, saved cisplatin from failure and assured that cisplatin would be approved by the FDA, as it was in 1978.”
– Today it has a 95% survival rate, even when it has spread widely across the body already.
Testicular cancer is commonly treated with combination therapy. The standard regimen is “BEP”, which consists of bleomycin, etoposide, and cisplatin. The type of therapy depends on several factors, including the type and location of the tumor, patient age, and other factors. In cases of metastatic testicular cancer, treatment is also determined by the sites of metastasis, the extent of disease, and other factors.
Survival rate strongly depends on the type of testicular cancer. The 95% refers to the 5-yr overall survival of metastatic testicular cancer, where metastasis is restricted to Lung/nodal (as it most commonly is).
Testicular cancer is also clustered into two different types: Seminoma and Non-Seminoma. For metastasis of Seminoma into the viscera, 5-yr overall survival is 88%. For metastasis of Non-Seminoma into the viscera, 5-yr overall survival is 67%.
Overall Survival (5 yrs) of Testicular Cancer as per the Risk Calculator:
https://www.oncotoolkit.com/calculator/igcccg-testicular-cancer-risk
#Testis + Non-Seminoma + Lung/Nodal = 96%
#Testis + Seminoma + Lung/Nodal = 95%
#Testis + Non-Seminoma + Viscera = 67%
#Testis + Seminoma + Viscera = 88%
#Capdevila, P., Aparicio Urtasun, J. Epidemiological patterns, temporal trends in management and long-term outcomes in testicular cancer: a 30-year single center experience. Clin Transl Oncol 28, 1374–1383 (2026).
https://doi.org/10.1007/s12094-025-04068-9
Quote: “This disease has become a model of curable neoplasm, mainly due to its exquisite sensitivity to cisplatin based combination chemotherapy and the development of a specialised multidisciplinary approach. Cure rates are now achievable for 95% of patients with testicular tumors, and 80% of those with metastatic disease. Despite its low mortality, optimizing management remains a key area of interest in oncology.”
#National Cancer Institute. Testicular Cancer Treatment (PDQ®)–Health Professional Version. Retrieved July 2026
https://www.cancer.gov/types/testicular/hp/testicular-treatment-pdq
Quote: “Testicular cancer is a highly treatable, usually curable cancer that most often develops in young and middle-aged men. Most testicular cancers are germ cell tumors. For treatment planning, germ cell tumors are broadly divided into seminomas and nonseminomas because they have different prognostic and treatment algorithms. For patients with seminomas (all stages combined), the cure rate exceeds 90%. For patients with low-stage seminomas or nonseminomas, the cure rate approaches 100%.[2-6]”
#Canadian Cancer Society. Chemotherapy for testicular cancer. Retrieved July 2026
https://cancer.ca/en/cancer-information/cancer-types/testicular/treatment/chemotherapy
Quote: “The most common chemotherapy combinations used to treat testicular cancer are:
BEP – bleomycin, etoposide (Vepesid) and cisplatin
EP – etoposide and cisplatin
VIP – etoposide, ifosfamide (Ifex) and cisplatin
[...] If testicular cancer doesn’t respond to drugs in earlier treatments or if the cancer comes back, you may be given another chemotherapy combination (called salvage chemotherapy). You may be offered one of the following combinations:
TIP – paclitaxel, ifosfamide and cisplatin
VIP – etoposide, ifosfamide and cisplatin
VeIP – vinblastine, ifosfamide and cisplatin.”
– And platinum drugs are a backbone of a large fraction of chemo therapies of all kinds.
#Brown A, Kumar S, Tchounwou PB. Cisplatin-Based Chemotherapy of Human Cancers. J Cancer Sci Ther. 2019
https://pmc.ncbi.nlm.nih.gov/articles/PMC7059781/
Quote: “Administered intravenously to humans, cisplatin is used as first-line chemotherapy treatment for patients diagnosed with various types of malignancies, such as leukemia, lymphomas, breast, testicular, ovarian, head and neck, and cervical cancers, and sarcomas.”
#Yusoh, N.A., Ahmad, H., Vallis, K.A. et al. Advances in platinum-based cancer therapy: overcoming platinum resistance through rational combinatorial strategies. Med Oncol 42, 262 (2025).
https://pmc.ncbi.nlm.nih.gov/articles/PMC12167724/
Quote: “Platinum-based cancer therapy remains a cornerstone of first-line treatment for several solid tumours such as ovarian, testicular, and non-small cell lung cancers, where it has received regulatory approval as both monotherapy and combination regimens.”
#Cancer History Project. Larry Einhorn, pioneer of platinum-based chemotherapy, discusses 50 years of cancer treatment innovation. 2024
– Cisplatin can be injected into a central venous access, a sort of hub that can be inserted easily and leads straight into the heart. Which means that it is immediately and rapidly distributed.
A “central venous (access) catheter” is a thin, flexible tube inserted into a large vein, usually in the chest or arm, that ends just above the heart. It is a standard administration technique for chemotherapy, allowing for continuous drug delivery without repeated needle sticks into smaller (e.g. arm) veins.
Depending on the patient, cisplatin can be administered in different ways. Typical for cisplatin is peripheral intravenous access, i.e. a needle in the arm. But the authors of this video had a central venous access catheter.
From Dr. Michal Chovanec (Comenius University, Bratislava) we received the following insight:
Quote: “[...] cisplatin can be given through central venous access, as in the narrator’s experience, but this is not universal. In testicular cancer, many experts prefer peripheral IV access when feasible, partly to avoid central-line complications such as thrombosis.”
#MacMillan Cancer Support. Central lines. Retrieved July 2026
Quote: “A central line is a long, thin hollow tube. It is put into a vein in your chest and used to give chemotherapy and other drugs.”
– Because Cisplatin is served ice cold, you can feel it spread all over your body, cooling you from the inside.
The unopened commercial bag of cisplatin is nowadays usually stored at room temperature. But the diluted infusion prepared by the pharmacy may be refrigerated before use depending on local pharmacy protocols and how long it will be stored.
#Electronic Medicines Compendium. Cisplatin 1mg/ml Injection BP. Retrieved July 2026
– The immediate effect is… nothing much. In the first few hours about 90% of the Cisplatin molecule binds to the plasma of your blood and is, for now, inactive.
In the blood, cisplatin predominantly binds to serum albumin, which is the most abundant protein in plasma.
#Wang J, Tao J, Jia S, Wang M, Jiang H, Du Z. The Protein-Binding Behavior of Platinum Anticancer Drugs in Blood Revealed by Mass Spectrometry. Pharmaceuticals (Basel). 2021
https://pmc.ncbi.nlm.nih.gov/articles/PMC7911130/
Quote: “After intravenous infusion, cisplatin rapidly diffuses into tissues, and more than 90% binds to plasma protein [20]. More specifically, 24 h after infusion, the protein-binding rate (PBR) for cisplatin is 98%, and the binding of platinum to protein is basically irreversible [21].”
– Over the next few days it is slowly being released from the plasma and showers your body with a constant barrage of poison.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “Following intravenous administration, plasma concentrations of cisplatin decay with an initial half-life of approximately 30 minutes and a terminal half-life of 24 hours (FDA, 1978; Gold and Raja, 2023). The half-life of total platinum is 5 days or longer (FDA, 1978). In a population PK model of patients treated with a 30-minute infusion of cisplatin, bound and unbound platinum had half-lives in plasma of 50 and 1.32 hours, respectively (Table 1) (Urien and Lokiec, 2004). One study measured urinary platinum concentrations 150 to 3022 days after cisplatin treatment and found two phases of renal platinum excretion with half-lives of 160 and 720 days (Schierl et al., 1995). Due to the high level of plasma protein and tissue binding, the rate at which plasma platinum concentrations decline is determined by the rate of degradation of platinum-bound plasma proteins and the rate of tissue regeneration (https://www.inchem.org/documents/pims/pharm/cisplat.htm).”
– All while your kidneys are working at maximum capacity to remove it from your body as quickly as they can so you can pee it out.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “The majority of cisplatin (>90%) is renally excreted, while a reduced amount is excreted via the saliva and bile (Chabner and Longo, 2001; https://www.inchem.org/documents/pims/pharm/cisplat.htm). Twenty-five percent of the cisplatin dose is excreted in the first 24 hours, while 43% is recovered in the urine by 5 days, mostly protein-bound (Table 1) (Chabner and Longo, 2001). Approximately 25% to 75% of cisplatin is excreted unaltered by the kidneys (https://www.inchem.org/documents/pims/pharm/cisplat.htm). The renal clearance of cisplatin and free/unbound/ultrafilterable platinum exceeds the CrCl and glomerular filtration rate (GFR), respectively, indicating that cisplatin and other platinum-containing compounds are actively cleared by the kidneys (FDA, 1978).”
– The 10% cisplatin that doesn't bind to plasma passes from your blood into your tissue and organs.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “Cisplatin is extensively distributed into body fluids and tissues with the greatest concentrations in the kidneys and liver (https://www.inchem.org/documents/pims/pharm/cisplat.htm). Cisplatin also distributes to the intestines, muscles, heart, adrenals, bladder, lungs, pancreas, spleen, lymph nodes, thyroid, gall bladder, thymus, cerebellum, cerebrum, testes, prostate, ovaries, and uterus (https://www.inchem.org/documents/pims/pharm/cisplat.htm). Without including intracerebral tumors, cisplatin concentrations in tumors are typically lower than the concentrations in the organ where the tumor is located (FDA, 1978). Platinum has additionally been found in leukocytes and erythrocytes (https://www.inchem.org/documents/pims/pharm/cisplat.htm). Maximum concentrations of platinum in red blood cells are reached within 90 to 150 minutes after an injection of cisplatin and decline in a two-phase manner with a half-life of 36 to 47 days (FDA, 1978).
Several cell membrane transporters have been associated with the transport of cisplatin and other platinum-containing products including CTR1, copper transporter 2 (CTR2), organic cation transporter 1 (OCT1), OCT2, MATE1, and P-type copper-transporting ATPases ATP7A and ATP7B (Ciarimboli, 2012). The specific tissue distribution of these transporters helps to explain why some tissues have higher cisplatin concentrations than others; e.g., OCT2 is selectively expressed on kidney basolateral membranes and OCT1 is most abundantly expressed in hepatocytes, explaining the high cisplatin concentrations observed in the kidneys and liver (Ciarimboli et al., 2005; Pelis and Wright, 2014; Chowdhury et al., 2016).
Cisplatin does not undergo the expected immediate and reversible drug-protein binding to plasma proteins (FDA, 1978). Cisplatin and platinum-containing products are quickly and widely bound to plasma and tissue proteins, including albumin, gamma-globulins, and transferrin. Plasma and tissue protein binding of cisplatin seems to be irreversible as bound platinum remains in the plasma throughout the lifespan of the albumin molecule. At least 90% of circulating platinum is bound to plasma proteins within the first 2 hours after a dose (Murry, 1997; O’Dwyer et al., 2000). Albumin-platinum complexes are gradually eliminated with a half-life of at least 5 days (FDA, 1978).”
– Where it finally enters your cells. The membranes of cells are well protected fortresses that carefully monitor who is allowed in but they can’t stop Cisplatin. It simply diffuses into the cell, with some of it even actively hauled in.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “Cisplatin enters cancer cells by passive diffusion or by active transport by organic cation transporters, including high-affinity copper uptake protein 1 (CTR1) (Ishida et al., 2002; Martinho et al., 2018). Cisplatin also enters cells via passive diffusion due to its neutral charge and small size (Hromas et al., 1987; Gately and Howell, 1993; Martinho et al., 2018).”
– Inside the cell, it sheds its chloride ions and connects to water molecules – like a grenade ejecting its safety. Cisplatin is now chemically active. Again, this should trigger emergency protocols – but thanks to its tinyness the poison escapes detection and passes through another line of defense: the nucleus, home of your DNA – here it finally causes catastrophic damage.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “In the cytoplasm, cisplatin undergoes hydrolysis to become a potent electrophile. Hydrolyzed cisplatin then enters the nucleus where it crosslinks DNA purine residues and subsequently forms adducts and consequential damage in the DNA strand, which eventually leads to apoptosis in cancer cells (Fig. 1) (Lippert, 1999).”
– Your DNA is a two meter long zipper, bundled up neatly and orderly.
#Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, Vitale L. On the length, weight and GC content of the human genome. BMC Res Notes. 2019
https://pmc.ncbi.nlm.nih.gov/articles/PMC6391780/
Quote: “The fact that very long molecules of human DNA can be contained, following accurate and multiple rounds of folding, within the very limited space of the nucleus, has always attracted attention. In 1990 when sequencing of human genome was just at its beginning, geneticist Jérôme Lejeune affirmed that “we have got 2 meters of so to speak magnetic tape in which everything is coded” (Louisiana Legislature, House Committee on the Administration of Criminal Justice, June 7, 1990). Traditionally, it has actually roughly been estimated over the last decades that the total length of human diploid DNA is around 2 m (Table 1) [7–13].”
– Cisplatin is like chewing gum that gets inside zipper teeth and hardens, clumping up parts that don’t belong together.
#Yimit, A., Adebali, O., Sancar, A. et al. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nat Commun 10, 309 (2019).
https://www.nature.com/articles/s41467-019-08290-2
Quote: “Once inside cells, cisplatin undergoes aquation, and the platinum atom of cisplatin binds covalently to the N7 position of purines resulting in about 65% GpG, 25% ApG 1,2-intra-strand crosslinks, and ~5–10% GpNpG 1,3- intra-strand crosslinks, as well as a lower percentage of inter-strand crosslinks5.”
#Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CFM. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics (Sao Paulo). 2018
“Cisplatin activation and DNA damage induction. A) The cisplatin activation process occurs by exchange of one or two of its chlorides for water molecules (monoaquated and diaquated, respectively). B) Cisplatin can form covalent bonds with DNA. The major DNA lesions are intrastrand DNA adducts and interstrand crosslinks (ICLs). The percentages represent the frequency of each type of DNA damage induced by cisplatin.”
– This is an emergency, because it critically interrupts the cell's ability to read and copy DNA. Your cell is now on an urgent timer: Fix this or die.
Cisplatin causes – among other things – a specific type of DNA-damage called “inter-strand crosslinks”, meaning different strands of DNA are glued to each other. This can potentially kill a cell if not repaired quickly.
#Huang, Y., & Li, L. (2013). DNA crosslinking damage and cancer - a tale of friend and foe. Translational Cancer Research
https://tcr.amegroups.org/article/view/1080/html
Quote: “DNA crosslinking damage occurs when crosslinking agents covalently connect two nucleotide residues from the same DNA strand (intrastrand crosslink) or from opposite strands [interstrand crosslink (ICL)]. Intrastrand crosslinks can be readily removed by the nucleotide excision repair (NER) mechanism (1). An ICL, however, constitutes an absolute block to DNA strand separation, thus interrupting essential DNA metabolic processes such as replication and transcription. Left unrepaired, ICLs can be extremely toxic especially in dividing cells, stalling DNA replication and leading to cell death.”
– Repair molecules spring into action but the chaos and damage is severe and very hard to fix.
#Yimit, A., Adebali, O., Sancar, A. et al. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nat Commun 10, 309 (2019).
https://www.nature.com/articles/s41467-019-08290-2
Quote: “In response to cisplatin, cells activate multiple repair pathways, among which nucleotide excision repair pathway constitutes the main mechanism to detect and repair cisplatin-induced DNA adducts6,7,8. Two major nucleotide excision repair pathways, transcription-coupled repair (TCR) and global repair (GR), are well known to remove cisplatin-induced DNA adducts. TCR acts on the transcribed strands (TS) of active genes, while GR acts on the non-transcribed region of the genome, as well as the non-transcribed strands (NTS) of transcribed genes9.”
#Huang, Y., & Li, L. (2013). DNA crosslinking damage and cancer - a tale of friend and foe. Translational Cancer Research
https://tcr.amegroups.org/article/view/1080/html
Quote: “DNA crosslinking damage occurs when crosslinking agents covalently connect two nucleotide residues from the same DNA strand (intrastrand crosslink) or from opposite strands [interstrand crosslink (ICL)]. Intrastrand crosslinks can be readily removed by the nucleotide excision repair (NER) mechanism (1). An ICL, however, constitutes an absolute block to DNA strand separation, thus interrupting essential DNA metabolic processes such as replication and transcription. Left unrepaired, ICLs can be extremely toxic especially in dividing cells, stalling DNA replication and leading to cell death.”
#Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CFM. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics (Sao Paulo). 2018
https://pmc.ncbi.nlm.nih.gov/articles/PMC6113849/
Quote: “ICLs are extremely cytotoxic, especially for proliferating cells, because ICLs covalently bind the two strands of the DNA helix together, which prevents strand separation and thereby inhibits vital cellular processes such as DNA replication and transcription 51. Invariably, replication of DNA containing ICLs induces DSBs, possibly due to collapse of the replication fork. The repair of ICLs is incredibly complex and involves numerous pathways, including NER, TLS, HR and Fanconi anemia (FA) proteins 52 (Figure 3B). Briefly, the XPF/ERCC1 nuclease complex cleaves one of the crosslinked strands, generating an intrastrand dinucleotide adduct 53. Subsequently, recombination proteins, including Rad51, Rad52, XRCC2, XRCC3, and RPA, generate a structure called a Holliday junction that is resolved by the MUS81/MMS4 complex 54. In addition to this pathway, the TLS process performed by the error-prone DNA polymerase η plays a significant role in ICL repair 52,55. Furthermore, corroborating the fact that cells from FA patients are sensitive to ICL-inducing agents, there is evidence indicating that the FA/BRCA pathway participates in both ICL and DSB repair by HR 56.”
– Cells that don’t need to divide quickly, say in your muscles, can slow down their metabolism, stop replicating and start repairing. Bit by bit they fix the genetic damage, removing the cisplatin. They will mostly be fine.
Cisplatin primarily targets rapidly dividing cells. They suffer from it the most, because the DNA damage interferes with their ability to make DNA copies during cell division.
Some cell types are known to divide slower than other cells. Skeletal muscle cells themselves actually cannot divide at all, they rely on specialized satellite (stem) cells to produce new muscle cells. Muscle cells are therefore expected to suffer less from cisplatin damage because they don’t constantly need to make copies of their DNA for cell replication.
#Gold JM, Patel P. Cisplatin. [Updated 2026 Jun 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK547695/
Quote: “Cisplatin chemotherapy is particularly effective at targeting rapidly dividing cells, as appreciated in rapidly growing malignant tumors.[20] Theoretically, cisplatin may not be as useful for slow-growing tumors.”
#Pabla N., Dong Z. Curtailing side effects in chemotherapy: a tale of PKCδ in cisplatin treatment. Oncotarget. 2012
https://www.oncotarget.com/article/439/text/
Quote: “Higher rate of DNA replication in rapidly proliferative cancer cells make them particularly sensitive to cisplatin-induced DNA damage. Depending on the amount of DNA damage, cancer cells either repair/tolerate the DNA damage or undergo apoptosis in case of extensive damage[8]. Identification of resistant cells that have higher DNA repair or reduced DNA damage response/apoptosis have provided the basis that DNA damage is the major mechanism of cisplatin-induced tumor cell death[8, 12].”
#Yoshimoto Y, Ikemoto-Uezumi M, Hitachi K, Fukada S and Uezumi A (2020) Methods for Accurate Assessment of Myofiber Maturity During Skeletal Muscle Regeneration. Front. Cell Dev. Biol.
Quote: “Skeletal muscle consists mainly of myofibers, which are large cylindrical cells with many nuclei. Myofibers are terminally differentiated post-mitotic cells; however, skeletal muscles possess a high ability to regenerate. Regeneration of mature myofibers is dependent on satellite cells. Satellite cells are mononucleated cells located between the plasma membrane of the myofiber and basal lamina. They normally remain in a quiescent state, but are activated upon muscle injury, and then they proliferate and differentiate to regenerate myofibers.”
– But there are cells that need to replicate quickly. The cells that make your hair grow, the lining of your gut, the tastebuds of your tongue, your bone marrow that makes red and white blood cells.
#Deconstructing mitosis in situ through 3D hair follicle reconstruction. J Cell Sci 15 February 2026
Quote: “Hair follicles are one of the most rapidly proliferating tissues in the body, but little is known about the ultrastructural organisation of mitosis within the intact epithelial niche.”
#Kaunitz JD, Akiba Y. Control of Intestinal Epithelial Proliferation and Differentiation: The Microbiome, Enteroendocrine L Cells, Telocytes, Enteric Nerves, and GLP, Too. Dig Dis Sci. 2019
https://pmc.ncbi.nlm.nih.gov/articles/PMC7211432/
Quote: “Some stem cells continually proliferate in adults, in particular the intestinal epithelium, which has the highest proliferation rate in the adult human body, with complete turnover normally occurring every 3–5 days.”
#Oura, N., Koyanagi-Matsumura, E., Hagimoto, A. et al. Tamoxifen triggers a transcriptional switch from proliferation to differentiation in the circumvallate taste epithelium in mice. Sci Rep 16, 2868 (2026)
https://www.nature.com/articles/s41598-025-32701-8
Quote: “The turnover rate of the taste epithelium is rapid. Taste bud cells have an average lifespan of 10–14 days43,44, with a half-life of about 11 days45, whereas the surrounding epithelial cells turnover even faster, with a half-life of about 2 days.”
#Higgins JM. Red blood cell population dynamics. Clin Lab Med. 2015
https://pmc.ncbi.nlm.nih.gov/articles/PMC4717490/
Quote: “The RBC population is in constant flux. About 2 million cells enter the bloodstream from the bone marrow of a typical healthy human adult every second, with about the same number being cleared.”
#MERCK MANUALS. Overview of White Blood Cell Disorders. Retrieved July 2026
Quote: “Normally, people produce about 100 billion white blood cells a day. The number of white blood cells in a given volume of blood is expressed as cells per microliter of blood. The total white blood cell count normally ranges between 4,000 and 11,000 cells per microliter (4 to 11 × 109 per liter).”
– All of them are factories producing new cells constantly and they now have a fundamental problem: Their internal replication clock doesn’t stop, their DNA needs to be copied and right now this is not possible.
#Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CFM. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics (Sao Paulo). 2018
https://pmc.ncbi.nlm.nih.gov/articles/PMC6113849/
Quote: “ICLs are extremely cytotoxic, especially for proliferating cells, because ICLs covalently bind the two strands of the DNA helix together, which prevents strand separation and thereby inhibits vital cellular processes such as DNA replication and transcription 51.”
– So if the damage is too heavy, apoptosis is triggered: programmed cell death. If a cell thinks it is damaged too much and destroys itself, this means it is working as intended. It sacrifices itself to protect the larger whole.
#Tanida S, Mizoshita T, Ozeki K, Tsukamoto H, Kamiya T, Kataoka H, Sakamuro D, Joh T. Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment. Int J Surg Oncol. 2012
https://pmc.ncbi.nlm.nih.gov/articles/PMC3384945/
Quote: “Cisplatin exerts its cytotoxic properties by reacting with DNA, which eventually culminates in irreversible apoptosis. Cisplatin primarily interacts with the N7-sites of purine residues in DNA to form DNA-DNA interstrand and intrastrand crosslinks [11]. The intrastrand adducts, ApG and GpG in particular, are responsible for the cytotoxic effects of cisplatin and account for 85–90% of the bound platinum [12]. These adducts block DNA replication and transcription. DNA adduct formation is followed by DNA damage recognition by over 20 proteins including hMSH2 of the mismatch repair (MMR) complex, the nonhistone chromosomal high-mobility groups 1 and 2 (HMG1 and 2) proteins and the transcriptional factor “TATA-binding protein” (TBP) [13–15]. The putative role of these DNA damage recognition proteins is to transmit DNA damage signals to downstream signaling cascades involving p53, MAPK, and p73, which ultimately induce apoptosis.
3.2. Cisplatin-Induced p53 and MAPK Activation
As mentioned above, cisplatin is believed to mediate activation of the p53 protein, a tumor suppressor, following DNA damage recognition. The transcriptional activation and stability of the p53 protein is known to be regulated by the two kinases ataxia telangiectasia-mutated protein (ATM) and ATM- and Rad3-related protein (ATR) [16, 17]. Cisplatin preferentially activates the ATR kinase which phosphorylates p53 on serine-15, resulting in its activation [18]. Of the mitogen-activated protein kinase (MAPK) signals that are involved in cisplatin-induced toxic effects, including extracellular signal-related kinases (ERKs), c-Jun N-terminal kinases (JNKs), and the p38 kinases, ERK activation appears to be the most important since activated ERK also phosphorylates p53 on serine-15 [19]. In addition, activation of JNK/p38 results in phosphorylation of the transcription factors c-Jun and activating transcription factor (ATF)-2 which, in turn, can bind to AP-1 binding sites in the promoters of multiple target genes. This cascade ultimately induces apoptosis through proapoptotic FasL gene expression.
3.3. Cisplatin Activation of p73-Dependent Apoptotic Signaling
p73 is a nuclear p53-related protein, which functions as a pro-apoptotic protein and accumulates in cisplatin-treated cells. Cisplatin-induced accumulation of p73 is dependent on MLH1 MMR proteins since it does not occur if the cells are deficient in these proteins [20]. Cisplatin-induced activation of the MMR protein-dependent p73 cell death pathway differs from its activation of p53 in that p73 activation does not involve ATR phosphorylation. The link between DNA damage recognition protein and activation of p73 may be the oncogenic tyrosine kinase c-Abl. Thus, cisplatin activates c-Abl, and accumulation of p73 following cisplatin treatment is not observed in c-Abl-defective cells. Cisplatin activation of c-Abl is regulated by MMR because MLH1-defective cells fail to activate c-Abl during cisplatin treatment. Furthermore, cisplatin cytotoxicity is reduced in c-Abl defective cells [21, 22]. The likely downstream events of both the cisplatin-induced p73 and p53 pathways are that cytochrome c is released through the mitochondrial membrane via Bax and Bak induction [23], which ultimately results in apoptosis through caspase 9 activation [6, 24] (Figure 1).”
– And now this is happening all over your body. Billions of cells start dying, creating all the side effects of chemotherapy.
#Thompson LE, Joy MS. Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury. J Pharmacol Exp Ther. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC11585315/
Quote: “As previously mentioned, cisplatin works by binding with DNA purine residues to form covalent adducts, which result in apoptosis. This occurs not only in the cancer cells but also in other organ systems, causing off-target, cytotoxic effects. Cisplatin treatment commonly causes nausea and vomiting, nephrotoxicity, ototoxicity, and neurotoxicity and less commonly cardiotoxicity and hepatotoxicity (Table 3) (Aldossary, 2019).”
#Rathinam, R., Ghosh, S., Neumann, W. et al. Cisplatin-induced apoptosis in auditory, renal, and neuronal cells is associated with nitration and downregulation of LMO4. Cell Death Discovery 1, 15052 (2015)
https://www.nature.com/articles/cddiscovery201552
Quote:“Ototoxicity, nephrotoxicity, and neurotoxicity are among the major side effects of cisplatin, a highly effective anti-neoplastic drug used in the treatment of solid tumors.1 Upon entering the cell, cisplatin is converted into a highly reactive intermediate by an aquation reaction, which eventually leads to the generation of reactive oxygen species and DNA damage, resulting in apoptosis and cell death. Although these processes facilitate a reduction in tumor size and/or prevent tumor growth, they adversely affect the normal cells in the inner ear, kidney, and nervous system. Studies indicate that more than 50% of patients treated with cisplatin develop hearing loss,2 70% manifest nephrotoxic effects,3 and 14–57% suffer from neurotoxic effects.4 These side effects limit the anti-cancer efficacy of cisplatin and significantly compromise the quality of life of cancer survivors. In the quest to mitigate these debilitating side effects, considerable progress has been made in delineating the signaling pathways that mediate the ototoxic, nephrotoxic, and neurotoxic effects of cisplatin.5–10 Though the underlying mechanisms are yet to be fully characterized, oxidative stress is widely recognized to play a causal role in the side effects of cisplatin.”
Cisplatin can cause many bad side effects. It is especially known for causing severe nausea and vomiting. The type and magnitude of side effects vary between patients. Anti-nausea and other drugs given alongside cisplatin can make side effects more bearable.
#Mayo Clinic. Cisplatin (intravenous route). Retrieved July 2026
https://www.mayoclinic.org/drugs-supplements/cisplatin-intravenous-route/description/drg-20062953
Quote: “Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
blood in urine or stools
burning, numbness, tingling, or painful sensations
change in frequency of urination or amount of urine
cough or hoarseness
difficulty in breathing
dizziness
drowsiness
feeling of fullness in the ears
fever or chills
increased thirst
loss of appetite
loss of balance
loss of hearing
lower back or side pain
nausea or vomiting
painful or difficult urination
pinpoint red spots on skin
ringing or buzzing in the ears
swelling of the feet or lower legs
trouble in hearing
unsteadiness or awkwardness
unusual bleeding or bruising
weakness in the arms, hands, legs, or feet”
– Which is the point, because your cancer cells are extremely not ready for any of this. As we’ve explained in detail before, cancer cells are broken cells. In a nutshell, their self destruction button is broken, they are really bad at fixing their own genetic damage and they literally can’t slow down.
The ability to resist apoptosis (programmed cell death), rapid mutations due to lack of or weaker DNA repair mechanisms, and rapid proliferation are some of the hallmarks of cancer cells.
#Hanahan D. Hallmarks of cancer—Then and now, and beyond. Cell, 2026
https://www.cell.com/cell/fulltext/S0092-8674(25)01498-9
Quote: “As a fundamentally expansive disease, sustaining proliferative signaling of cancer cells is an obvious hallmark capability, one that is deeply embedded in our knowledge base about cancer. A majority of cancers contain activating mutations or chromosomal rearrangements in genes—dubbed oncogenes—that serve to chronically sustain otherwise transitory cell proliferation via triggering and stimulating progression through the cell division cycle. Most prominent is KRAS, which—via activating point mutations—upregulates a complex intracellular signaling network that, among other things, drives chronic proliferation. KRAS is mutated in ∼30% of human tumors, including pancreatic adenocarcinoma (90%), colorectal cancer (50%), and lung adenocarcinoma (35%). Beyond KRAS and its homologs NRAS and HRAS, other commonly mutated proliferation-inducing “driver” oncogenes include PIK3CA, BRAF, and BCR-ABL. Other genes can become oncogenes by virtue of gene amplifications and other rearrangements, including often-circular extrachromosomal DNA elements (ecDNA), which collectively serve to induce/overexpress wild-type growth-stimulating proteins. Examples include MYC, CCND1, EGFR, and EGFR2/HER2, although the latter two can also be mutationally activated in certain cancer types. Most notably, the MYC gene, encoding a heterodimeric transcription factor (TF) that regulates thousands of genes, is amplified/rearranged, or its antagonists deleted, in 40% of human tumors. Other tumors lacking structural changes in the MYC gene locus have evidence for increased MYC expression and transcriptional activity by upregulation of its expression or post-translational modifications. Currently, 193 genes have been defined as proliferation-driving oncogenes by virtue of mutational alteration in human tumors and functional validation in model systems, as reported in the COSMIC database (Catalog of Somatic Mutations in Cancer) (Table S1). The precise mechanistic contributions of these non-canonical mutant genes to this and other hallmark capabilities are diverse and the subject of continuing investigation.
[...] A qualitatively distinct anti-proliferative cancer hallmark involves circumventing protective mechanisms that serve to eliminate aberrant or damaged cells—including cancer cells—via the induction of regulated pathways of cell suicide collectively termed “programmed cell death.” Apoptosis is the prototype and most broadly operative form of programmed cell death across the spectrum of human cancers. In brief, indirect sensing of certain forms of cellular and genomic damage and abnormality can trigger either a paracrine (extrinsic) or an autocrine (intrinsic) program leading to apoptotic cell death. The extrinsic program involves signaling by secreted ligands from abnormality-sensing cells that activate “death receptors” of the tumor-necrosis family that in turn induce a cascade of degradative proteases (caspases) leading to cancer cell death. By contrast, the intrinsic program involves an increase in expression of so-called BH3-only proteins (PUMA, BIM, and NOXA) that act by binding to the effector proteins BAX and BAK at the mitochondrial outer membrane to initiate the apoptotic death pathway, which culminates in mitochondrial depolarization, caspase activation, and cellular disintegration. Levels of three gatekeepers, the anti-apoptotic proteins BCL-2, BCL-XL, and/or MCL-1, counterbalance the pro-apoptotic abnormality sensors, keeping cells alive by sequestering BH3-only proteins and their downstream effector proteins BAX and BAK. Upregulation of the gatekeepers is one mechanism by which cancer cells limit apoptotic cell death, as is mutational inactivation or gene deletion of TP53, whose loss otherwise triggers apoptosis by transcriptional upregulation of PUMA and NOXA.
[...] The foundation of cancer as a chronically expansive disease lies in the loss of genomic integrity. There are multiple manifestations of this phenotypic characteristic across the spectrum of cancer types, ranging from point mutations to amplifications, rearrangements, and deletions of genes and chromosomal domains; gains and losses of entire chromosomes (or arms); and the generation and persistence of linear and circular ecDNA, as well as whole genome doubling and genome shattering (chromothripsis). As noted above, telomere erosion and dysfunction prior to telomere stabilization by telomerase or ALT fuels this genomic disarray during tumorigenesis, facilitated by deficiencies in DNA damage-sensing and repair pathways, most prominently involving defects in mismatch repair and homologous recombination. The resulting disruptions in genome integrity elicit changes in gene expression and/or activity that convey hallmark capabilities.”
We also made a whole video about why cancer cells are hard to kill. Check it out here:
– Most testicular cancer cells are born from germ cells. Specialists made for the reproduction of the whole, gigantic organism.
#Lobo J, Acosta AM. An update on testicular sex cord stromal tumours: recent advances and diagnostic pearls. Diagnostic Histopathology. 2026
https://www.sciencedirect.com/science/article/abs/pii/S1756231726000393
Quote: “Over 90% of testicular cancers derive from germ cells, more specifically from germ cell precursors originating in the extraembryonic mesoderm of the yolk sac, being classified as ‘testicular germ cell tumors’ (TGCTs).1 TGCTs emerge as a consequence of multiple factors, including predisposing genetic variants and environmental insults that hamper proper development or promote transformation of germ cell precursors and germ cells at different developmental stages.2 The second largest group of testicular tumors is significantly less understood and comprises neoplasms that derive from (or show differentiation to) sex cord derivatives and/or elements of the testicular stroma. These represent 4–8% of all testicular tumors3,4 and are classified under the broad category of ‘testicular sex cord-stromal tumors’ (TSCSTs).5”
#National Cancer Institute. NCI Dictionary of Cancer Terms. Germ Cell. Retrieved August 2026
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/germ-cell
Quote: “germ cell [...] A cell that develops into a reproductive cell, which is an egg in females and a sperm in males.”
– Reproduction is the whole point for all living things, so the responsibility is huge. For germ cells the integrity of their DNA is a critical priority – even small mistakes could introduce genetic damage into the bloodline and weaken it. So they constantly scan themselves and tolerate almost no errors.
Germ cells carry genetic information to the next generation, so many systems bias toward avoiding mutation, even at the cost of killing damaged germ cells. Note that some of this is only known from animal experiments.
From Dr. Michal Chovanec (Comenius University, Bratislava) we received the following insight:
Quote: “Testicular cancer arises from germ cells. These are normally designed for reproduction where DNA integrity is especially important and almost no errors are tolerated. First, the germ cells have very low tolerance for DNA damage and their capacity for DNA repair is very low here."
#Bloom, J.C., Loehr, A.R., Schimenti, J.C. and Weiss, R.S. (2019), Germline genome protection: implications for gamete quality and germ cell tumorigenesis. Andrology
https://onlinelibrary.wiley.com/doi/10.1111/andr.12651
“Undifferentiated spermatogonia must maintain genomic integrity in order to prevent reproductive failure or transmission of deleterious mutations to progeny. Studies in mice have shown that undifferentiated spermatogonia are highly sensitive to DNA damage (van Beek et al., 1990; van der Meer et al., 1992). When compared to differentiated spermatogonia committed to meiosis, undifferentiated spermatogonia in mice lack foci of DNA damage-sensing proteins γH2AX and MDC1 after IR exposure. In studies using 53BP1 foci to examine DSB repair dynamics in murine tissues, undifferentiated spermatogonia not only had a slightly lower induction of DSBs after IR compared with somatic cells but also significantly slower repair kinetics (Ahmed et al., 2007; Rübe et al., 2011).”
#Bloom JC, Schimenti JC. Sexually dimorphic DNA damage responses and mutation avoidance in the mouse germline. Genes Dev. 2020
https://pmc.ncbi.nlm.nih.gov/articles/PMC7706705/
Quote: “Germ cells specified during fetal development form the foundation of the mammalian germline. These primordial germ cells (PGCs) undergo rapid proliferation, yet the germline is highly refractory to mutation accumulation compared with somatic cells. Importantly, while the presence of endogenous or exogenous DNA damage has the potential to impact PGCs, there is little known about how these cells respond to stressors. To better understand the DNA damage response (DDR) in these cells, we exposed pregnant mice to ionizing radiation (IR) at specific gestational time points and assessed the DDR in PGCs. Our results show that PGCs prior to sex determination lack a G1 cell cycle checkpoint. Additionally, the response to IR-induced DNA damage differs between female and male PGCs post-sex determination. IR of female PGCs caused uncoupling of germ cell differentiation and meiotic initiation, while male PGCs exhibited repression of piRNA metabolism and transposon derepression. We also used whole-genome single-cell DNA sequencing to reveal that genetic rescue of DNA repair-deficient germ cells () leads to increased mutation incidence and biases. Importantly, our work uncovers novel insights into how PGCs exposed to DNA damage can become developmentally defective, leaving only those genetically fit cells to establish the adult germline.”
– When Cisplatin wrecks their DNA they are unusually willing to push their kill switch and die, to prevent damaged material being passed on to the next generation.
From Dr. Michal Chovanec (Comenius University, Bratislava) we received the following insight:
Quote: "Second, if there is the DNA damage, the kill switch (apoptosis) is triggered rather than risking propagation of damaged genetic material. And testicular cancer, luckily, inherited this biology feature as its fatal flaw. When cisplatin damages the DNA, the cancer cells are unusually willing to self-destruct."
#de Vries G, Rosas-Plaza X, van Vugt MATM, Gietema JA, de Jong S. Testicular cancer: Determinants of cisplatin sensitivity and novel therapeutic opportunities. Cancer Treat Rev. 2020
https://www.sciencedirect.com/science/article/pii/S030573722030092X
Quote: “Cisplatin sensitivity
With the introduction of cisplatin-based chemotherapy in the 1970s, cure rates of metastatic TC have improved drastically [39]. Even though cisplatin has been used in the clinic for a long time, the mechanisms behind the excellent sensitivity of these tumor types remain elusive. Two features of TC tumors that have been related to cisplatin sensitivity of TC are: insufficient DNA repair of cisplatin-induced DNA damage, and a hypersensitive apoptotic response, both discussed below and summarized in Fig. 1, Fig. 2.”
#Matthias Gutekunst, Thomas Mueller, Andrea Weilbacher, Michael A. Dengler, Jens Bedke, Stephan Kruck, Moshe Oren, Walter E. Aulitzky, Heiko van der Kuip; Cisplatin Hypersensitivity of Testicular Germ Cell Tumors Is Determined by High Constitutive Noxa Levels Mediated by Oct-4. Cancer Res 1 March 2013
Quote: “Cisplatin-based chemotherapy has been a successful cure for TGCT for decades. A variety of molecular determinants of these neoplasms were proposed to account for their exquisite sensitivity to cisplatin such as a reduced DNA repair capacity, a deregulated G1–S transition or marginal p21 expression (2, 3, 21). Much of the research done in this field has focused on p53, which is almost exclusively expressed in its wild-type conformation in TGCTs (22). We recently showed a central role for p53 in TGCT hypersensitivity to cisplatin and suggested an intrinsic sensitivity of these tumors to activation of p53, which leads to robust induction of apoptosis in this specific cellular context (10). In the present study, we found that this sensitivity is dependent on the presence of Oct-4, although p53 activation is not directly influenced by this mediator of pluripotency. Rather, by maintaining high constitutive Noxa protein levels, Oct-4 provides a cellular context that primes TGCT cells to p53-dependent apoptosis.”
– The tumor collapses, no matter where in the body it has escaped to.
Here we mean that cisplatin can trigger apoptosis/tumor cell death even in distant metastatic locations throughout the body.
#Köberle B, Usanova S, Piee-Staffa A, Heinicke U, Clauss P, Brozovic A, Kaina B. Strong apoptotic response of testis tumor cells following cisplatin treatment. Int Urol Nephrol. 2024
https://pmc.ncbi.nlm.nih.gov/articles/PMC10853295/
Quote: “Most solid metastatic cancers are resistant to chemotherapy. However, metastatic testicular germ cell tumors (TGCT) are cured in over 80% of patients using cisplatin-based combination therapy. Published data suggest that TGCTs are sensitive to cisplatin due to limited DNA repair and presumably also to a propensity to undergo apoptosis. To further investigate this aspect, cisplatin-induced activation of apoptotic pathways was investigated in cisplatin-sensitive testis tumor cells (TTC) and compared to cisplatin-resistant bladder cancer cells. Apoptosis induction was investigated using flow cytometry, caspase activation and PARP-1 cleavage. Immunoblotting and RT-PCR were applied to investigate pro- and anti-apoptotic proteins. Transfections were performed to target p53- and Fas/FasL-mediated apoptotic signaling. Immunoblotting experiments revealed p53 to be induced in TTC, but not bladder cancer cells following cisplatin. Higher levels of pro-apoptotic Bax and Noxa were observed in TTC, anti-apoptotic Bcl-2 was solely expressed in bladder cancer cells. Cisplatin led to translocation of Bax to the mitochondrial membrane in TTC, resulting in cytochrome C release. Cisplatin increased the expression of FasR mRNA and FasL protein in all tumor cell lines. Targeting the apoptotic pathway via siRNA-mediated knockdown of p53 and FAS reduced death receptor-mediated apoptosis and increased cisplatin resistance in TTC, indicating the involvement of FAS-mediated apoptosis in the cisplatin TTC response. In conclusion, both the death receptor and the mitochondrial apoptotic pathway become strongly activated in TTC following cisplatin treatment, explaining, together with attenuated DNA repair, their unique sensitivity toward platinum-based anticancer drugs.”
– And then the immune system sweeps in and cleans up.
Across many tumour models and some clinical settings, cisplatin not only kills cancer cells but also boosts anti‑tumour immune responses.
But also, from Dr. Michal Chovanec (Comenius University, Bratislava) we received the following insight:
Quote: "[...] careful not to imply that immune killing is the main reason cisplatin cures testicular cancer. The central mechanism is cisplatin-induced DNA damage followed by apoptosis in unusually sensitive germ cell tumor cells. Immune involvement may contribute, but I would keep the main emphasis on DNA damage and apoptosis."
#Andreas R. de Biasi, Jonathan Villena-Vargas, Prasad S. Adusumilli; Cisplatin-Induced Antitumor Immunomodulation: A Review of Preclinical and Clinical Evidence. Clin Cancer Res 1 November 2014
Quote: “Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (i) MHC class I expression upregulation; (ii) recruitment and proliferation of effector cells; (iii) upregulation of the lytic activity of cytotoxic effectors; and (iv) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy's antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy. Clin Cancer Res; 20(21); 5384–91. ©2014 AACR.”
#Elham Beyranvand Nejad, Tetje C. van der Sluis, Suzanne van Duikeren, Hideo Yagita, George M. Janssen, Peter A. van Veelen, Cornelis J.M. Melief, Sjoerd H. van der Burg, Ramon Arens; Tumor Eradication by Cisplatin Is Sustained by CD80/86-Mediated Costimulation of CD8+ T Cells. Cancer Res 15 October 2016
Quote: “Certain cytotoxic chemotherapeutic drugs are immunogenic, stimulating tumor immunity through mechanisms that are not completely understood. Here we show how the DNA-damaging drug cisplatin modulates tumor immunity. At the maximum tolerated dose (MTD), cisplatin cured 50% of mice with established murine TC-1 or C3 tumors, which are preclinical models of human papillomavirus (HPV)-associated cancer. Notably, the curative benefit of cisplatin relied entirely upon induction of tumor-specific CD8+ T cells. Mechanistic investigations showed that cisplatin stimulated tumor infiltration of inflammatory antigen-presenting cells (APC) expressing relatively higher levels of the T-cell costimulatory ligands CD70, CD80, and CD86. Cell death triggered by cisplatin was associated with the release of at least 19 proteins in the tumor environment that could act as damage-associated molecular patterns and upregulate costimulatory molecules, either alone or in concert, but the responsible proteins remain unknown. Essentially, the curative effect of cisplatin was abrogated in mice lacking expression of CD80 and CD86 on APCs. Furthermore, cisplatin treatment was improved by CTLA-4 blockade, which increases the availability of CD80/86 to bind to CD28. In contrast, there was no effect of CD27 stimulation, which replaces CD70 interaction. At the cisplatin MTD, cure rates could also be increased by vaccination with synthetic long peptides, whereas cures could also be achieved at similar rates at 80% of the MTD with reduced side effects. Our findings reveal an essential basis for the immunogenic properties of cisplatin, which are mediated by the induction of costimulatory signals for CD8+ T-cell–dependent tumor destruction. Cancer Res; 76(20); 6017–29. ©2016 AACR.”
– The side effects were not fun and I’ll spare you the details. But I want you to know that just in the last few years drugs against chemo side effects have improved massively. They made the experience bearable.
Chemotherapy drugs, such as cisplatin and others, can have many side-effects. Drugs can be given to alleviate these side effects. In general, chemotherapy is still very hard on the body but its side-effects have become somewhat more tolerable in recent decades, through the use of anti-side-effect medicine.
#Amjad MT, Chidharla A, Kasi A. Cancer Chemotherapy. [Updated 2023 Feb 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK564367/
Quote: “The side effects of cancer chemotherapy can be acute or prolonged and may need monitoring. In addition, it would require multi-disciplinary monitoring as specific patient populations may be at higher risk for complications.
Management of common side effects of chemotherapy:
Infusion reactions, from hypersensitivity reactions: Management options include using pre-medications like diphenhydramine, methylprednisolone, epinephrine
Chemotherapy-induced nausea and vomiting: Treatment options include prochlorperazine, haloperidol, metoclopramide, lorazepam, dexamethasone, ondansetron, granisetron, dolasetron, palonosetron, dronabinol, aprepitant, fosaprepitant. Palonosetron has a longer half-life, better efficacy, and higher binding affinity than granisetron.[19]
Mucositis: Using magic mouthwash, avoidance commercial mouthwashes, and lemon glycerin swabs
Fatigue: Interventions like exercise, optimizing sleep quality, and behavioral therapies such as relaxation can help fatigue.
Chemotherapy-induced diarrhea: Using agents like loperamide, diphenoxylate, atropine, and octreotide.
Chemotherapy-induced constipation: Using agents like docusate, senna, milk of magnesia, bisacodyl, lactulose, polyethylene glycol, enemas
Neurotoxicity: Using agents like vitamin B6, glutamine, gabapentin, pregabalin, carbamazepine, or tricyclic antidepressants (amitriptyline).”
– The anti nausea drugs worked so well I didn’t have to vomit once.
Cisplatin can cause many bad side effects. It is especially known for causing severe nausea and vomiting. The type and magnitude of side effects vary between patients. Anti-nausea and other drugs given alongside cisplatin (or other chemotherapy drugs) can make side effects more bearable.
#Mayo Clinic. Cisplatin (intravenous route). Retrieved July 2026
https://www.mayoclinic.org/drugs-supplements/cisplatin-intravenous-route/description/drg-20062953
Quote: “Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
Black, tarry stools
blood in urine or stools
burning, numbness, tingling, or painful sensations
change in frequency of urination or amount of urine
cough or hoarseness
difficulty in breathing
dizziness
drowsiness
feeling of fullness in the ears
fever or chills
increased thirst
loss of appetite
loss of balance
loss of hearing
lower back or side pain
nausea or vomiting
painful or difficult urination
pinpoint red spots on skin
ringing or buzzing in the ears
swelling of the feet or lower legs
trouble in hearing
unsteadiness or awkwardness
unusual bleeding or bruising
weakness in the arms, hands, legs, or feet”
#CancerCare. Understanding and Managing Chemotherapy Side Effects. 2018
https://media.cancercare.org/publications/original/24-ccc_chemo_side_effects.pdf
Quote: “Chemotherapy-Induced Nausea and Vomiting (CINV)
When chemotherapy enters the body, sensors in the digestive system and brain detect its presence as a foreign substance. In a complex series of signals among the brain and the mouth, stomach, small intestine and bloodstream, the medication stimulates the “vomiting center” in the brain. Several chemicals, including ones called serotonin and substance P, are released, triggering the nausea and vomiting reflex. This is the body’s effort to get rid of the foreign substance. Some people experience nausea and vomiting side effects from chemotherapy within the first few hours of receiving chemotherapy. Doctors call this reaction “acute nausea and vomiting.” Other patients don’t feel symptoms the day of chemotherapy but may develop nausea and vomiting during the next few days. This condition is called “delayed nausea and vomiting.” You shouldn’t assume that nausea and vomiting that occurs a day or two after treatment isn’t related to chemotherapy. It’s important to tell your doctor or nurse when you experience these symptoms, no matter when they occur. Because some people getting chemotherapy expect to feel ill, they may start experiencing symptoms even before their treatment begins. This is referred to as “anticipatory nausea and vomiting.” Sometimes, the sights, sounds or smells of the treatment room can trigger this reaction.
Treating Nausea and Vomiting
There are anti-nausea medications that your doctor will decide to prescribe based on the type of chemotherapy you are getting and how much nausea and vomiting might be expected. Sometimes, patients receive anti-nausea drugs intravenously (through a needle inserted into a vein). Other anti-nausea medications are available in pill or liquid form to take by mouth, as a skin patch or as a suppository (a soft cone—or cylinder-shaped capsule containing medication that dissolves in the rectum). After chemotherapy, you may also be given anti-nausea medications to take at home. It’s important to understand how these drugs should be taken. To prevent CINV, some medications are designed to be taken for several days, whether you feel nauseous or not. Others are meant to be taken only when you feel nauseous. If you have questions about when you should take your anti-nausea medication, be sure to call your doctor or nurse.”
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