Small molecules in combination with conventional chemotherapeutic drugs: Light at the end of the tunnel?

Recent studies have shown BI2536 and bortezomib to be effective in squamous cell carcinoma of the head and neck (SCCHN) cell lines. In this systemic in vitro study, we examined the antitumor effect of the small molecules BI2536 and bortezomib in combination with cisplatin or docetaxel in nine squamous cell carcinoma cell lines, most of head and neck origin. Dose escalation studies were performed with these cell lines using bortezomib, BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and the Human Apoptosis Array kit. The combination of bortezomib and BI2536 with cisplatin or docetaxel showed a significantly higher antiproliferative and apoptotic activity in all SCCHN cell lines investigated compared with single agent cisplatin or docetaxel alone (P≤0.021). Combination of conventional chemotherapeutic drugs, such as cisplatin and docetaxel, with small molecules in the clinical setting may enhance the antitumor activity of these agents and may lead to less toxic side-effects and a more effective cancer therapy.