HSP90 inhibition in differentiated thyroid cancer

~Dose-limiting toxicity has restricted the use of kinase inhibitors in differentiated thyroid cancer. Gild et al. have taken advantage of the role of the heat shock protein HSP90 in mediating the effect of kinases such as RET, AKT and BRAF to investigate an alternative mechanism to downregulate these pathways. HSP90 regulates protein degradation of these kinases, and is overexpressed in cancer cells. The action of an HSP90 inhibitor AUY922 against medullary and papillary thyroid cancer (PTC) cell lines expressing a RET mutation was studied in vitro. AUY922 inhibited MAPK and mTOR signalling and induced apoptosis in vitro, and enhanced radioactive iodine uptake in the PTC cell line. The latter effect is particularly significant given the reduced iodine avidity of such tumours clinically. AUY922 is in trials for non-small cell lung cancer, and the authors propose streamlining into thyroid cancer trials. Read the full article in Endocrine Connections 5 10-19 (OA)