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Significance The treatment of cancer is highly reliant on drug combinations. Next-generation, targeted therapeutics are demonstrating interesting single-agent activities in clinical trials; however, the discovery of companion drugs through iterative clinical trial-and-error is not a tenable mechanism to prioritize clinically important combinations for these agents. Herein we describe the results of a large, high-throughput combination screen of the Bruton’s tyrosine kinase inhibitor ibrutinib versus a library of nearly 500 approved and investigational drugs. Multiple ibrutinib combinations were discovered through this study that can be prioritized for clinical examination.

proceedings of the national academy of sciences of the united states of america

High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell–like diffuse large B-cell lymphoma cells