SMAC mimetic combined with conventional chemotherapy agents yields synergy in the treatment of non-small cell lung cancer

4884 Standard chemotherapy for non-small cell lung cancer often uses doublet combinations of cisplatin or carboplatin with gemcitabine, paclitaxel, docetaxel, vinorelbine, or etoposide. While clinical responses and survival benefits are seen these are very modest and new more effective therapies are needed. As one approach to this problem we recently developed a small molecule mimetic of SMAC, a mitochondrial protein that inhibits the inhibitors of apoptosis proteins (IAPs) as a potential new chemotherapy agent (Li L, et. al. Science. (2004) 305: 1471-1474). Here we explore SMAC mimetic as a potential therapy for NSCLC, as well as the benefits of using it in conjunction with traditional chemotherapies. We tested 50 non-small cell lung cancer lines (NSCLCs) for their in vitro sensitivity to the SMAC mimetic or combined with other chemotherapy agents in a 96 hour MTS assay. Most NSCLC lung cancer lines were completely resistant to treatment with the SMAC mimetic alone (IC50 >>10μM). However, 10/50 NSCLC lines were killed by the SMAC mimetic alone at IC50s