The role of TRAP1, the mitochondrial Hsp90 in cancer progression and as a possible therapeutic target

Hsp90, a 90 kDa heat shock protein (HSP), is a molecular chaperone involved in various cellular processes. It is highly conserved across species and plays a critical role in protein folding quality control, protein degradation and, most importantly, stabilizing proteins against heat stress. Emerging evidences suggest that HSPs accumu-late not only in stressful conditions, but also in patho-physiological conditions and tumours. They play a role in refolding partially damaged functional proteins and also stabilize cell survival factors. Studies also suggest the role of organelle-specific Hsp90 chaperones in these processes, which further adds to the complexity. These findings make the Hsp90 family a potent target for anti-cancer drugs. Tumour necrosis factor receptor -associ-ated protein 1 (TRAP1), the mitochondrial homolog of Hsp90, is found to play a pivotal role in mitochondrial bioenergetics, maintenance of mitochondrial integrity and mounting stress responses. Tumour cells exhibit a peculiar phenotype known as the Warburg effect, where they evade the mitochondrial oxidative phosphorylation and produce ATP by aerobic glycolysis. Studies suggest TRAP1 as a key regulator in this metabolic switchover along with a pivotal role in drug resistance and anti-apoptotic effects. This article discusses the molecular mechanisms of TRAP1 to regulate cancer growth, its role in protecting cells from apoptosis and toxicity from anti-cancer drugs. The possibility of TRAP1 as a poten-tial target for cancer therapies in the near future based on new-age therapeutic strategies by inhibiting the pro-tein is also discussed here.