Abstract B20: Discovery of combination therapies in a pan-cancer context through functional complementarity and convergence analysis of oncogenic drivers

Inherent genetic alterations and tissue-specific variations in cancer present a range of unique vulnerabilities which can be targeted by precision cancer therapies. An understanding of these alterations is a crucial first step in developing novel therapeutic hypotheses in a personalized context. An unbiased method to correlate responses to treatment with small-molecules is cancer cell line (CCL) sensitivity profiling. This allows the understanding of single-agent therapies and associated mechanisms of resistance by employing unbiased combination screening. However, performing such studies in a principled manner to understand multiple potential combinations is limited by the large scale of the required experiments. The area under the concentration-response curve can be used as a measure of sensitivity and the relationship between the sensitivity profiles for a large number of drugs helps build a network based on similarity of activity. Hence, it would be possible to identify ‘modules' or ‘clusters' that correspond to small molecules with highly correlated response across a number of cell lines. However, these clusters are often non-informative in predicting or determining potential combinatorial treatments. By leveraging recent whole-exome and RNA sequencing efforts across a diverse panel of human cancer cell lines coupled with small-molecule sensitivity information, this study aims at applying a pan-cancer exome-wide approach to identify potentially synergistic dr...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Finding Synthetic Lethal Interactions through Functional Genomics: Poster Presentations - Proffered Abstracts Source Type: research