24.02.1 The Special Characteristics of Cancer Cells

It is the special characteristics of cancer cells that has been, and is still, the key to the development of pharmacological agents used to treat the disease. These characteristics include uncontrolled proliferation, dedifferentiation of cancer cells resulting in loss of function, invasiveness and the development of metastases.

In many cancer cells, the mechanisms of cell proliferation are not subject to the same regulatory processes found in non-cancerous cells. This leads to uncontrolled cell proliferation that usually results in an increase in cell multiplication although a reduction can also occur. Interruption of proliferative control leading to cancer generally occurs as a consequence of genetic changes or mutations. In particular (i) inactivation of genes, known as tumour suppression genes, that have the ability to suppress malignant changes and includes p53, pRB1, PTEN and CD95 and; (ii) activation of genes, known as protooncogenes, which normally control cell division, into tumour producing oncogenes and includes Src, Abl and Ros. Uncontrolled proliferation arising from these gene mutations leads to changes in growth factor signalling, in cell cycle function and in apoptosis (programmed cell death). To date, over 200 tumour suppression genes and protooncogenes have been discovered and shown to be involved in the evolution of cancers such as retinoblastoma, breast carcinoma, colon carcinoma, squamous cell carcinoma and chronic myelogenous leukaemia.

Cellular dedifferentiation occurs when there is a loss in the ability of progeny cells to carry out normal programmed cellular function, as a result of problems caused by faulty parent cells. Cancers caused by dedifferentiating cells are quick growing and have a poorer prognosis than well differentiated cancers.

Under normal conditions, cells tend not to be found outside their designated tissue of origin. Therefore liver cells are restricted to the liver, cortical neurones restricted to the brain and so on. Any cells escaping from their tissue location tend to undergo programmed cell death (apoptosis). However, cancer cell lose the ability to undergo apoptosis and can invade other cells within the tissue. For example, in rectal cancer, cancerous mucosal epithelial cells can invade other cell layers of the rectum due their ability to secrete metalloproteinase enzymes that destroy the extracellular matrix. These translocated cells, coupled with a loss of apoptotic factors can lead to the formation of aggressive tumours.

Lastly, secondary tumours called metastases are formed by cancer cells that have been released from the initial primary site and transported to other sites via blood or the lymphatic system. Metastases are the principal cause of morbidity (the incidence of a disease) and mortality (death from the disease).