TRAP1 and its therapeutic potential

The mitochondrial Hsp90 isoform, Tumor Necrosis Factor Receptor Associated Protein 1 (TRAP1), is central to the pathogenesis of disease states that include cancer, ischemic retinopathy, and diabetic kidney disease among others. TRAP1 contributes to these diseases through the regulation of mitochondrial metabolism, apoptosis, oxidative stress, cell signaling and angiogenesis through interactions with client proteins. Numerous TRAP1-selective inhibitors have been developed to limit the toxicities associated with Hsp90 pan-inhibition, while leveraging the therapeutic benefits of TRAP1 inhibition. This review focuses on these inhibitors and the potential clinical uses of TRAP1-directed therapies.