Predicting anti-cancer drug synergy using extended drug similarity profiles

Abstract

Combination therapy is a promising strategy for confronting the complexity of cancer. However, experimental exploration of the vast space of potential drug combinations is costly and unfeasible. Therefore, computational methods for predicting drug synergy are much-needed for narrowing down this space, especially when examining new cellular contexts. Here, we thus introduce CCSynergy, a flexible, context-aware and integrative deep learning framework that we have established to unleash the potential of the Chemical Checker extended drug similarity profiles for the purpose of drug synergy prediction. We have shown that CCSynergy enables predictions of superior accuracy, remarkable robustness and improved context-generalizability as compared to the state-of-the-art methods in the field. Having established the potential of CCSynergy for generating experimentally validated predictions, we exhaustively explored the untested drug combination space. This resulted in a compendium of potentially synergistic drug combinations on hundreds of cancer cell lines, which can guide future experimental screens.