Poly(ADP-Ribose) Polymerase Inhibitors

Abstract

This session not only described several poly(ADP-ribose) polymerase (PARP) inhibitors but also included talks on the science of nuclear excision repair, an oxidized glutathione, and a heat shock protein (HSP) 90 inhibitor. SUMMARY OF PRESENTATIONS Science of Nuclear Excision Repair Dr. George Simon opened the session by presenting the science of nuclear excision repair. He reviewed preclinical data, including evidence that apoptosis increases in cell lines exposed to cisplatin when excision repair cross-complementation group 1 (ERCC1) siRNA is added. He also reviewed clinical data from the International Adjuvant Lung Trial, in which improved survival with adjuvant cisplatin-based chemotherapy was restricted to tumors with low ERCC1. 1 He then focused on trials that designed to tailor therapy to repair genes. The Spanish Customized Adjuvant Treatment trial randomly assigns postresection patients with positive N1 or N2 nodes to docetaxel cisplatin or an experimental arm. Based on data correlating higher breast cancer 1 (BRCA1) mRNA levels with cisplatin resistance and docetaxel sensitivity, 2 the experimental arm assigns treatment by quartile expression for BRCA1 (lowest: gemcitabine cisplatin; 2‐3: docetaxel cisplatin; and highest: docetaxel). The TAilored post-Surgical Therapy in Early-stage NSCLC (TASTE) trial randomizes postsurgical patients to cisplatin pemetrexed or an experimental arm. In the experimental arm, mutations in the epidermal growth factor receptor (EGFR) lead to treatment with erlotinib, whereas treatment for EGFR wild-type patients are assigned based on ERCC1 status (cisplatin pemetrexed versus observation). He then discussed the MADe IT Trail, in which patients with metastatic disease were assigned treatment regimen based on ERCC1 and ribonucleotide reductase M1 (RRM1) levels (Figure 1). Outcomes in this trial exceeded selected historical controls, and the difference was more apparent for