VIEWS IN THE SPOTLIGHT Bcl-2 Inhibition or FBXW7 Mutation Sensitizes Solid Tumor Cells to HDAC Inhibition In Vitro but Could Prove Diffi cult to Validate in Patients

Summary: In this issue of Cancer Discovery, He and colleagues determined that Mcl-1 levels are a key factor in the response to histone deacetylase (HDAC) inhibitors, and FBXW7 mutation is a biomarker for sensitivity to HDAC inhibition. They also present evidence for synergy between treatment with HDAC inhibitors and Bcl-2– targeted therapeutics. These data provide an exciting new biomarker and combination therapy that should be evaluated clinically. Cancer Discov; 3(3); 258–9. ©2013 AACR. See related article by He et al., p. 324 (4). Head and neck squamous cell carcinoma (HNSCC) is composed of a diverse group of tumors from the upper aero-digestive tract with poor survival, few useful biomarkers, and even fewer targeted therapeutics ( 1). Recent genomic analyses of HNSCC have identifi ed many genomic alterations in this disease ( 2, 3), but the majority of these events do not lend themselves directly to targeted therapeutic intervention (i.e., TP53 mutation). This leaves the path toward novel targeted treatments still uncertain