Heat shock protein 90 inhibition: rationale and clinical potential

Heat shock protein 90 (HSP90) is a molecular chaperone protein essential for cellular survival. Functionally, HSPs promote proper protein folding, prevent misfolding, and restore three-dimensional protein structure which is critical following toxic cellular stresses. Recently, targeting HSP90 pharmacologically has gained traction in cancer therapy. Oncogenic cells depend on their ability to withstand endogenous (anoxia, nutrient deprivation, pH changes, and deranged signaling pathways) and exogenous (chemotherapy and radiation therapy) stressors for survival. Pharmacological inhibition of HSP90 destabilizes proteins and leads to degradation through the proteasome. This article will review the utility of HSP90 inhibition, as well as the current adoption in clinical trials and practice.