Uses of labeled HSP90 inhibitors

摘要

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).

主权项

1. A method for determining whether a patient with a blood cancer will likely respond to therapy with an HSP90 inhibitor which comprises:
(a) contacting a sample containing blood cancer cells and non-cancerous blood cells from the patient with a cell permeable fluorescently labeled HSP90 inhibitor that binds directly and preferentially to a cancer-specific form of HSP90 present in the cancer cells of the patient; (b) measuring the amount of fluorescently labeled HSP90 inhibitor bound to HSP90 protein in the cancer cells and non-cancer cells in the sample; and (c) comparing the amount of the fluorescently labeled HSP90 inhibitor bound to the cancer cells with the amount of the fluorescently labeled HSP90 inhibitor bound to the non-cancer cells,wherein a greater amount of fluorescently labeled HSP90 inhibitor bound to the cancer cells than the non-cancer cells indicates presence of the cancer specific form of HSP90 in the cancer cells; thereby determining that the blood cancer will likely respond to therapy with the HSP90 inhibitor.