Abstract

Engineering Reversal of Drug Resistance in Cancer Cells

Shantanu Chowdhury, Professor, IGIB

One of the hurdles in the treatment/management of cancer is development of resistance towards conventional therapies. We explored a model involving parallel analyses of (a) drug-specific gene signatures and (b) gene expression changes associated with cancer progression. Drug-specific gene modules were developed from drug activity of 1400 chemically defined compounds and expression profiles of about 21,000 different genes in 60 cell lines from eight cancer types. Next, we analysed >600 patient-derived tumor gene expression datasets across four cancer types (breast, lung, colon and ovary) to identify significantly associated regulators of cancer progression. Based on this computational models were built that enabled us to first predict and then validate in experimental cellular models that genetic perturbation can be used to reverse drug resistance in aggressive cancer cells. Insights from this proof-of-concept study will be discussed.