Inhibiting the Inhibitors of Apoptosis: When Two Targets Are Better Than One

Summary: In this issue of Cancer Discovery, Pullarkat and colleagues present the results from a phase I clinical trial that is the first to combine small-molecule inhibitors for multiple antiapoptotic proteins, BCL2 as well as BCL-XL, with a traditional chemotherapy backbone for patients with relapsed/refractory acute lymphoblastic leukemia. This trial has demonstrated impressive response rates with acceptable toxicity while providing proof of concept that dual targeting—hitting BCL2 hard and BCL-XL soft—is both effective and tolerable in a heterogeneous patient population with prior existing cytopenias. See related article by Pullarkat et al., p. 1440.