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Development of Combination Targeted Therapies for Multi-Driver Cancers

Gongqin Sun

Most cancers are supported by multiple independent drivers, and cannot be effectively treated by targeted therapies blocking any one driver. Instead, combination targeted therapy which uses a combination of targeted drugs to block all important drivers is required. Developing combination targeted therapies for such cancers requires an understanding of the complex interactions between targeted drugs and the individual drivers as well as other unintended targets. The current pharmacological models, based on the Hill equation, do not adequately describe such complex interactions. This article discusses the general approaches of developing combination targeted therapies, and comments on a recently developed biphasic pharmacological model for characterizing such complex interactions and predicting synergistic drug combinations for multi-driver cancers.