Combination chemotherapy for head and neck cancer: the addition of Bcl-2 inhibitors.

Locoregionally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) lacks a validated therapeutic approach. Evidence emphasizes the importance of Bcl-2, Bcl-XL and survivin as survival factors in HNSCC cells. Targeting the Bcl-2 system is therefore an attractive strategy for restoring a 'normal' apoptotic process in HNSCC, making cells more susceptible to conventional chemotherapy and disrupting neovascularization. Among Bcl-2 inhibitors, non-peptidic small molecules hold substantial promise in HNSCC adjuvant therapy. Predicting treatment response requires the precise profiling of tumors, ideally by the use of panels that include markers from different pathways; the further definition of such panels may benefit from proteomic and/or pharmacogenomic approaches. Furthermore, in combination treatments, the effect of drug delivery sequence requires further investigation.