顺铂耐药的分子机制
摘要
Cisplatin is widely used in the clinical treatment of many types of solid tumors. The cytotoxicity of cisplatin is primarily mediated by its binding to DNA followed by the DNA damage response and the induction of apoptosis. However, the cisplatin-based chemotherapy is often limited by the intrinsic or acquired drug resistance. During the past 30 years, intense researches have been conducted on the cisplatin resistance and the understanding about the molecular mechanisms has largely arisen. There are several mechanisms responsible for cisplatin resistance and the process of the drug resistance appears to be multifactorial. In this review, we systematically describe and discuss these mechanisms, including the reduced intracellular accumulation of cisplatin, the increased drug detoxification, the alterations in DNA repair and DNA damage response and apoptosis pathways as well as the changes of indirect signal pathways.