Natural Products for the Treatment of Never Smoker Lung Cancer

Lung cancer arising in never smokers, those that have smoker less than 100 cigarettes in a lifetime, represent ~15-20% of all new lung cancer cases in the USA. These cancers are responsible for ~300,000 deaths annually world-wide, with an increased incidence in women and those of East Asian origin. Genome wide studies have shown that tumors from patients that have never smoked have significantly fewer mutations than lung cancers arising in smokers, however, many of these mutations are in key driver genes that could be targeted. To that end, we are using a panel of non-small cell lung cancer cell lines that are derived from patients in the never smoker classification and have molecular signatures of never smoker lung cancer to discover novel therapeutics to target these tumors. Our approach is to use a library of natural products from marine-derived bacteria, a rich resource of unique chemistry, coupled with the never smoker lung cancer cell lines to probe therapeutic chemical/biological interactions. We have already screened 8,000 natural product fractions against four of these never smoker cell lines to identify promising biological signatures. We will progress active natural products through a series of biological assays, mechanism of action studies and bioinformatics to provide a link between a chemical and a genetic biomarker to predict sensitivity. The results from these studies will be disseminated to the academic and clinical community as well as to the general public as appropriate.