Sloan-Kettering Institute for Cancer Research

Cornell University

Erica M Gomes-Dagama

Gabriela Chiosis

Tony Taldone

Mary L Alpaugh

Jason S Lewis

Steven M Larson

Naga Vara Kishore Pillarsetty

Monica L Guzman

Hongliang Zong

Nagavarakishore Pillarsetty

This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.

Uses of labeled HSP90 inhibitors

The disclosure provides evidence that the abundance of this particular 'oncogenic HSP90' species, which is not dictated by HSP90 expression alone, predicts for sensitivity to HSP90 inhibition therapy, and thus is a biomarker for HSP90 therapy. The disclosure also provides evidence that identifying and measuring the abundance of this oncogenic HSP90 species in tumors predicts of response to HSP90 therapy. 'Oncogenic HSP90' is defined herein as the HSP90 fraction that represents a cell stress specific form of chaperone complex, that is expanded and constitutively maintained in the tumor cell context, and that may execute functions necessary to maintain the malignant phenotype. Such roles are not only to regulate the folding of overexpressed (i.e. HER2), mutated (i.e. mB-Raf) or chimeric proteins (i.e. Bcr-Abl), but also to facilitate scaffolding and complex formation of molecules involved in aberrantly activated signaling complexes (i.e. STATS, BCL6).

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New Rochelle, NY, United States of America

Erica M Gomes-Dagama