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Molecular Mechanisms of Chemoresistance and Cytotoxicity Associated with Platinum Drugs
Li Yinyan, Wang Xiujun*
Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310058, China
Abstract: Cisplatin， carboplatin and oxaliplatin have been used clinically for treatment of many types of cancers， including ovarian， cervical， lung， colorectal cancer and relapsed lymphoma. Platinum-DNA adducts are formed following the uptake of the drug into the cell nucleus. As a result， DNA structure is changed， leading to the disorder of DNA replication and transcription， and eventually the cell death. Treatment with platinum agents is characterized by resistance and toxicity through activating a number of signal transduction pathways. This article highlights recent discoveries in cellular pathways responsive to the platinum agents， and provides a molecular basis for understanding the differences in clinical application， cytotoxicity and drug resistance among the platinum anticancer drugs.
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