Nagaraju GP, et al. - Given that client proteins of heat shock protein 90 (HSP90) such as hypoxia induced factor-1α (HIF-1α) have a central role in the mechanisms of resistance of pancreatic ductal adenocarcinoma (PDAC) to radiotherapy and chemotherapy, researchers undertook this investigative evaluating inhibition of HSP90 as a therapeutic strategy for radiosensitization in pancreatic cancer. In the setting of PDAC, they evaluated ganetespib, a selective inhibitor of HSP90, as a radio-sensitizer. In vivo in nude mice bearing HPAC xenograft tumors confirms the potentiation of the antitumor effects of chemoradiotherapy by ganetespib and modulation of key pathways (eg HIF-1α, STAT3, and AKT). The data emphasize HIF-1α-mediated mechanisms of HSP90 inhibition that sensitize PDAC cells to chemoradiotherapy.