The Anticancer Drug AUY922 Generates a Proteomics Fingerprint That Is Highly Conserved among Structurally Diverse Hsp90 Inhibitors

AUY922 is a potent synthetic Hsp90
antagonist that is moving steadily
through clinical trials against a small range of cancers. To identify
protein markers that might measure the drug’s effects, and
to gain understanding of mechanisms by which AUY922 might inhibit
the proliferation of leukemia cells, we characterized AUY922’s
impacts on the proteomes of cultured Jurkat cells. We describe a robust
and readily assayed proteomics fingerprint that AUY922 shares with
the flagship Hsp90 inhibitors 17-DMAG and radicicol. We also extend
our proteomics findings, demonstrating that an unrelated antagonist
of protein folding potentiates the antiproliferative effects of AUY922.
Results provide a set of candidate biomarkers for responses to AUY922
in leukemia cells and suggest new modalities for enhancing AUY922’s
anticancer activities.