New Activity of HSP90 Inhibitors Inducing Down Regulation of ZAP-70 and Inducing Apoptosis in Leukemia Cells
This invention provides the first evidence that Hsp90 plays an active role in CLL progression/prognosis. Inhibiting Hsp90 or ZAP-70 activity or disrupting the interaction between the two molecules directs otherwise resistant cells to undergo apoptosis. Hsp90 inhibitors (proprietary or those available in the art) can induce cancer cell apoptosis through the directed down regulation of ZAP-70. Hsp90 inhibition leads to the specific down regulation of pathological ZAP-70 in leukemic cells without down regulating ZAP-70 in natural killer cells or healthy T-cells.
A method and compositions useful to modulate apoptosis in a cell. Treatment of patients with CLL or other cell proliferative disorders. Prophylaxis in patients with high risk to develop leukemias. Determination of cancer risk factors and biological analysis of important signaling pathways in leukemia. A method for the identification of novel Hsp90 “client” proteins. A method for early diagnosis of CLL and other cancers. In vitro test that can be used as a clinical prognostic factor, based upon the detection of active Hsp90 complexes and the induction of apoptosis. This prognostic assay is amenable to high throughput automatization and could be applied to other types of normal or malignant cells.
This invention provides new uses of specific inhibitors of heat shock protein 90 (Hsp90) to induce apoptosis of leukemic cells. Additionally, this technology provides a clinical prognostic marker in cancer cells, based on the detection of apoptosis in vitro and the identification of active Hsp90 complexes.
Patent Number: US8741578B2
Application Number: US2007666899A
Inventor: Castro, Januario E. | Kipps, Thomas J. | Prada, Carlos E.
Priority Date: 2 Nov 2004
Priority Number: US8741578B2
Application Date: 4 Oct 2007
Publication Date: 3 Jun 2014
IPC Current: G01N003353 | G01N0033574
US Class: 4350071 | 43500721 | 43500723
Assignee Applicant: The Regents of the University of California
Title: Methods of detecting chronic lymphocytic leukemia with Hsp90 and ZAP-70
Usefulness: Methods of detecting chronic lymphocytic leukemia with Hsp90 and ZAP-70
Summary: (M1) is useful for determining the prognosis or diagnosis of a subject at risk for a cell proliferative disorder such as leukemia, where the subject is a mammal, preferably a human. (M2) is useful for detecting chronic lymphocytic leukemia (CLL). (M3) is useful for modulating apoptosis in a cell, preferably neoplastic cell. (M4) is useful for treating leukemia, preferably CLL in a subject (claimed).
Novelty: Determining prognosis/diagnosis of subject at risk for cell proliferative disorder, involves determining presence of heat shock protein 90-Zeta associated protein-70 complex and/or amount of activated Hsp90 in cell expressing ZAP-70
診斷/治療
癌症/腫瘤
8741578
State Of Development This technology is offered exclusively or nonexclusively for U.S. and/or certain foreign countries. A commercial sponsor for potential future research is sought. Related Materials Tech ID/UC Case 19596/2005-094-0 Related Cases 2005-094-0
美國
