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Review
. 2009 Dec;12(6):148-52.
doi: 10.1016/j.drup.2009.09.001. Epub 2009 Oct 4.

Novel strategies for reversing platinum resistance

Mian M K Shahzad  1 , Gabriel Lopez-Berestein, Anil K Sood
Affiliations
Review

Novel strategies for reversing platinum resistance

Mian M K Shahzad et al. Drug Resist Updat. 2009 Dec.

Abstract

Platinum-based drugs continue to be the mainstay of therapy for ovarian cancer. Along with adverse effects, chemoresistance (intrinsic or acquired) has become a major limitation in the management of recurrent disease. Even though much is known about the effects of platinum drugs on cancer cells, the mechanisms underlying resistance are poorly understood. In this review, we summarize the current data on chemoresistance and discuss novel strategies to reverse resistance to platinum-based drugs. The most important targets highlighted here include Aurora kinases, PARP, ATP7B, and ERCC1. Furthermore, we discuss the implications of these novel approaches for ovarian cancer treatment.

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Figures

Fig. 1
Fig. 1. Mechanisms of platinum resistance in cancer cells
Cisplatin (CDDP) enters cell by Ctr1 or diffusion and leads to DNA damage and cell death. Cisplatin resistance may evolve through the following pathways: A) cisplatin can be pumped out of the cell by ATP7B. B) Nucleotide excision repair pathway (NER) and C) PARP repair of DNA damage. D) Aurora kinases may protect cells against chemotherapy by blocking apoptosis; E) ECM produces favorable changes in tumor microenvironment that inhibit chemotherapy-induced apoptosis
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