Inhibition of DNA damage response and PI3K signaling has emerged as a potential strategy for treating triple-negative breast cancer (TNBC). Hong and colleagues assessed a CHK1 inhibitor, prexasertib, in combination with a PI3K/mTOR inhibitor, samotolisib, in preclinical models and a phase Ib study. This combination was synergistic or additive in 30 of 38 PDX models examined. In the clinical setting, an overall response rate (ORR) of 15.1% was observed. However, the toxicity profile of this combination limits its utility moving forward. Given the potential clinical benefit of the combined inhibition of CHK1 and PI3K/mTOR, alternative strategies to more safely target these pathways in patients are needed.

Although immune checkpoint inhibition has provided clinical benefit to cancer patients, many patients do not ultimately respond to this strategy; thus, new strategies to enhance the efficacy of ICI are needed. Papadopoulos and colleagues performed a phase I study of an anti-GITR monoclonal antibody,...

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