Striving for synergy: how to improve cancer immunotherapy through multiple agonist costimulation

The mainstay therapies for patients with advanced cancer have long been radiation and chemotherapeutics that exact substantial adverse effects on healthy tissue. Fortunately, the recent revolution in our understanding of the molecular, biochemical and immunological properties of tumors has facilitated the development of rational approaches that target tumors, but not healthy cells, with greater precision. An excellent example is the development of small molecule inhibitors that target an oncogenic driver mutation in the BRAF signaling protein expressed within the majority of melanomas [1]. Although BRAF inhibitors produce impressive clinical responses with minimal adverse effects owing to its specificity for mutant but not wild-type BRAF, tumor clones that acquire additional oncogenic mutations typically cause disease recurrence, thus necessitating the development of additional small molecules targeting these secondary mutations [2].

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