Banerji, U. (2009) Heat Shock Protein 90 as a Drug Target: Some Like It Hot. CLINICAL CANCER RESEARCH, 15 (1). pp. 9-14. ISSN 1078-0432

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Abstract

Heat shock protein 90 (HSP90) is a ubiquitously expressed chaperone that is involved in the posttranslational folding and stability of proteins. Inhibition at the NH2-terminal ATP-binding site leads to the degradation of client proteins by the ubiquitin proteasome pathway. Inhibition of HSP90 leads to the degradation of known oncogenes, such as ERB-B2, BRAF, and BCR-ABL, leading to the combinatorial blockade of multiple signal transduction pathways, such as the RAS-RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase and phosphatidylinositol 3-kinase pathways. Multiple structurally diverse HSP90 inhibitors are undergoing early clinical evaluation. The clinical focus of these drugs should be solid tumors, such as breast, prostate, and lung cancers, along with malignant melanoma, in addition to hematologic malignancies, such as chronic myeloid leukemia and multiple myeloma. HSP90 inhibitors can be used as single agents or in combination with other targeted treatments or conventional forms of treatment such as chemotherapy and radiotherapy. Clinical trials evaluating efficacy of these agents should include innovative designs to capture cytostasis evidenced by clinical nonprogression and enrichment of patient populations by molecular characterization. The results of clinical trials evaluating the efficacy of drugs targeting this exciting target are awaited.

Item Type:	Article
Authors (ICR Faculty only):	Banerji, Udai
All Authors:	Banerji, U.
Uncontrolled Keywords:	BREAST-CANCER CELLS; CHEMOTHERAPY-INDUCED APOPTOSIS; REFRACTORY ADVANCED CANCERS; SCHEDULE-DEPENDENT MANNER; HSP90 MOLECULAR CHAPERONE; TUMOR BIOLOGY MATTERS; PHASE-I; ANDROGEN RECEPTOR; HEAT-SHOCK-PROTEIN-90 INHIBITOR; GROWTH-FACTOR
Research teams:	ICR divisions > Clinical Studies > Clinical Pharmacology – Adaptive Therapy ICR divisions > Cancer Therapeutics > Clinical Pharmacology – Adaptive Therapy
Depositing User:	Users 10 not found.
Date Deposited:	16 Feb 2009 15:56
Last Modified:	20 Mar 2018 14:14
URI:	http://publications.icr.ac.uk/id/eprint/7461

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