Modeling cellular responses in non-small cell lung cancer using marine derived natural products

Using a group of well annotated non-small cell lung cancer (NSCLC) cell lines (mutation status, gene expression profiling, siRNA profiling) selective and non-selective cytotoxic natural products can be identified based upon data of the sensitive cell lines. We have focused our efforts on discovery of natural products from marine-derived bacteria through the screening of a collection of ˜6500 natural product fractions. A screen of the 6500 natural product fractions against 27 non-small cell lung cancer cell lines has revealed a number of promising fractions.

Target identification predictions can be made based upon cell line data of sensitive and non-sensitive cell lines, thereby allowing for further prioritization of natural product fractions. LCMS and NMR data is combined with the bioinformatics and screening data to allow for better prioritization of natural product fraction leads. The lead fractions are further analyzed to identify known and novel compounds of interest. Biological activities are then followed up with further cytoxicity and mechanistic studies of the natural product against NSCLC cell lines. Representative biomarkers of both resistant and sensitive NSCLC cell lines are also identified. This has led to a number of insights into the sensitivities of cancers based upon their mutation status.