HDAC inhibitors with PD-1 blockade: a promising strategy for treatment of multiple cancer types?

In one of the most significant breakthroughs in cancer treatment, recent studies have demonstrated the ability of immunotherapy involving blockade of CTLA-4 and PD-1 checkpoint receptors on T cells to induce deep and durable anti-tumor responses [1]. PD-1 blockade is an especially promising approach with activity across multiple cancer types. However, the actual response rates are relatively low, for example, approximately 20% in unselected lung cancer patients [2,3]. In addition, many patients who initially benefit from this treatment eventually progress. Consequently, there is an urgent need to develop new combinatory approaches to enhance and sustain benefit from PD-1 blockade. A variety of agents are being considered for combining with anti-PD-1, including blocking mAb to other checkpoint receptors, agonistic mAb to stimulate T-cell responses and various vaccine based approaches [1].

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