On June 23, 2015 Synta Pharmaceuticals reported the publication in this month’s issue of Cancer Immunology Research of an in-depth review describing the rationale for pursuing the combination of Hsp90 and immune checkpoint inhibition for cancer therapy (Press release, Synta Pharmaceuticals, JUN 23, 2015, View Source [SID:1234505793]). Schedule your 30 min Free 1stOncology Demo! The review article, titled "Targeting Heat-Shock Protein 90 (Hsp90) as a Complementary Strategy to Immune Checkpoint Blockade for Cancer Therapy," is available online at View Source Synta is currently studying the Hsp90 inhibitor ganetespib in several randomized studies, including the GALAXY-2 trial, a global, randomized, multi-center Phase 3 study of ganetespib and docetaxel for the second-line treatment of advanced non-small cell lung adenocarcinoma. Know more, wherever you are: The review article describes preclinical findings that suggest that proteasomal degradation of cellular client proteins associated with Hsp90 inhibition may augment antitumor immune response through increased cellular antigen expression and subsequent enhanced T-cell recruitment and tumor-cell recognition. The review article also explains that client proteins affected by Hsp90 inhibition include oncogenes that may drive expression of Programmed Death-Ligand 1 (PD-L1), a key immune checkpoint. The resulting reduction of PD-L1 expression on tumor cells may increase T-cell mediated cytotoxic activity and complement the activity of selective anti-PD-1 or anti-PD-L1 antibody therapies. This is supported by in vivo study results, where ganetespib was found to potentiate the antitumor efficacy of anti-PD-L1 antibody treatment. In these studies, the combination of ganetespib and an anti-PD-L1 antibody displayed significantly greater antitumor activity than either individual agent, in mouse models of both colon carcinoma and melanoma.
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"While there is still more to learn regarding the mechanistic basis for combining Hsp90 and immune checkpoint inhibitors, and the role of Hsp90 in antitumor immunity, the findings in this review suggest that this approach may be complementary and therapeutically advantageous. We look forward to exploring the combination of immune checkpoint inhibitors and ganetespib in future clinical studies," said Chen Schor, President and Chief Executive Officer of Synta. "Our team and collaborators are also conducting preclinical studies investigating potential combinations of ganetespib and other emerging forms of immunotherapy for cancer, including T-cell therapy. We are encouraged by our progress thus far and will look to present and publish results of these studies in the future."