Detecting the Potential Pharmacological Synergy of Drug Combination by Viability Assays In Vitro.

Heat shock protein 90 (HSP90) is a molecular chaperone necessary for the folding and proper function of multiple "client" proteins. HSP90 is involved in numerous biological processes and is critical to maintain proteostasis and to protect the cells from potentially harmful environmental stresses such as heat. However, in cancer, the role of HSP90, and other molecular chaperones, is corrupted as many of HSP90 clients are kinases and transcription factors whose aberrant activation or mutation drives tumor growth. Thus, developing a polytherapy, or combination therapy, that includes an HSP90 inhibitor in addition to targeting an oncogene or oncogenic pathway is an appealing therapeutic approach. This protocol will provide detailed methods on how to assess the potential synergy of polytherapy by viability assays in vitro.