INTRODUCTION

An Overview of Platinum-Based Chemotherapy

Platinum-based chemotherapy uses coordination complex of platinum to treat cancer. Over 40 years ago, cisplatin become the first platinum (Pt) compound approved by US Food and Drug Association (FDA) for treatment of testicular cancer, ovarian cancer and bladder cancer. Other approved platinum-based chemotherapy includes cisplatin, carboplatin, and oxaliplatin. These platinum compounds are expanded to treat more cancer types and have become one of the major chemotherapy regimens.

Approved Platinum-Based Anti-Cancer Drugs

N7 position of guanine

Mechanism

Platinum compounds mainly target DNA and cause DNA damage including DNA mono-adduct, intrastrand, interstand crosslink, and DNA-protein crosslinks. The electrophilic behavior of these compound react with nucleophilic residues of DNA, especially on N7 position of guanine. Platinum-induced lesions are extremely toxic as they block essential DNA transactions such as replication and transcription.

Intrastrand crosslink Interstrand crosslink Mono-adduct DNA-protein crosslink

Challenges

Platinum-based chemotherapy kills cancer cells by damaging nuclear DNA that triggers apoptosis. However, the efficacy has always been a problem due to drug resistance. Treatment of platinum-based anti-cancer drugs triggers multiple molecular or cellular responses. One of the inherent resistances lies in the endogenous cellular responses to the damages and DNA repair pathways that remove damages from the targets.

In this project, we investigated the gene set enrichment of different biological pathways in 2 different global gene expression datasets produced by microarray experiments on cells treated with or without platinum-based anti-cancer drugs including carboplatin and cisplatin. We expect to see enriched gene expression in related DNA repair pathways in treated groups compared with control groups.

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