VIEWS IN THE SPOTLIGHT Testing the Metal of ERCC2 in Predicting the Response to Platinum-Based Therapy

Summary: DNA repair has been shown to affect the cellular response to platinum-based therapy in a variety of cancers; however, translating this knowledge to the clinic has proven diffi cult and yielded mixed results. In this issue of Cancer Discovery, Van Allen and colleagues have analyzed responders and nonresponders to neoadjuvant platinum-based therapy with locally advanced urothelial cancer and identifi ed a series of mutations in the nucle-otide excision repair (NER) gene ERCC2 that correlate with the response to platinum-based therapy. This work provides evidence that defects in NER can be exploited to maximize the effi cacy of conventional platinum-based chemotherapy. Cancer Discov; 4(10); 1118–9. ©2014 AACR. See related article by Van Allen and colleagues, p. 1140 (8). It has been estimated that 750,000 patients per year will receive a platinum (Pt)-based chemotherapy in the treatment of their cancer. Although Pt-based chemotherapy is curative in a small subset of cancers, most tumors show a mixed response. The ability to predict which patients will respond and which will not has been the subject of intense study in many cancers, with mixed results. Pt-based agents impart their clinical effi cacy vi