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Platinum Resistance: The Role of DNA Repair Pathways

Authors' Affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Requests for reprints: Lainie P. Martin, Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. E-mail: Lainie.Martin{at}fccc.edu.

Abstract

Although platinum chemotherapeutic agents such as carboplatin, cisplatin, and oxaliplatin are used to treat a broad range of malignant diseases, their efficacy in most cancers is limited by the development of resistance. There are multiple factors that contribute to platinum resistance but alterations of DNA repair processes have been known for some time to be important in mediating resistance. Recently acquired knowledge has provided insight into the molecular mechanisms of DNA repair pathways and their effect on response to chemotherapy. This review will discuss the most important DNA repair pathways known to be involved in the platinum response, i.e., nucleotide excision repair (NER) and mismatch repair (MMR), and will briefly touch on the role of BRCA in DNA repair. The therapeutic implications of alterations in DNA repair which affect response to platinum in the treatment of patients with malignant disease, such as excision repair cross-complementation group 1 (ERCC1) deficiency and mismatch repair deficiency, will be reviewed.