Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers Journal Article
| Authors: | Jhaveri, K.; Taldone, T.; Modi, S.; Chiosis, G. |
| Article Title: | Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers |
| Abstract: | Hsp90 is an ATP dependent molecular chaperone protein which integrates multiple oncogenic pathways. As such, Hsp90 inhibition is a promising anti-cancer strategy. Several inhibitors that act on Hsp90 by binding to its N-terminal ATP pocket have entered clinical evaluation. Robust pre-clinical data suggested anti-tumor activity in multiple cancer types. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma. In breast cancer, proof-of-concept was demonstrated by first generation Hsp90 inhibitors in combination with trastuzumab mainly in human epidermal growth factor receptor 2 (HER2). +. metastatic breast cancer. There are a multitude of second generation Hsp90 inhibitors currently under investigation. To date, however, there is no FDA approved Hsp90 inhibitor nor standardized assay to ascertain Hsp90 inhibition. This review summarizes the current status of both first and second generation Hsp90 inhibitors based on their chemical classification and stage of clinical development. It also discusses the pharmacodynamic assays currently implemented in clinic as well as other novel strategies aimed at enhancing the effectiveness of Hsp90 inhibitors. Ultimately, these efforts will aid in maximizing the full potential of this class of agents. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). © 2011 Elsevier B.V. |
| Keywords: | treatment response; unclassified drug; constipation; fatigue; review; cisplatin; advanced cancer; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; hypertension; monotherapy; side effect; solid tumor; unspecified side effect; antineoplastic agents; clinical trials as topic; paclitaxel; anorexia; neoplasm; neoplasms; imatinib; unindexed drug; melanoma; bortezomib; liver toxicity; multiple myeloma; breast cancer; anemia; lung non small cell cancer; nausea; thrombocytopenia; vomiting; peripheral neuropathy; qt prolongation; nucleoside analog; antineoplastic activity; cytotoxicity; drug structure; drug screening; drug synthesis; kidney carcinoma; hodgkin disease; docetaxel; abdominal pain; dizziness; dyspnea; prostate cancer; rash; cancer inhibition; hyponatremia; clinical study; lymphoma; heat shock protein 90 inhibitor; tanespimycin; heat shock protein 90; hsp90 heat-shock proteins; nausea and vomiting; hypoglycemia; carcinoid; targeted therapy; headache; taxane derivative; dna topoisomerase inhibitor; trastuzumab; aphasia; drug dose increase; anthracycline; breast metastasis; chronic lymphatic leukemia; visual disorder; drug binding; supraventricular tachycardia; drug formulation; 5 (2,4 dihydroxy 5 isopropylphenyl) 4 (4 morpholinomethylphenyl) 3 isoxazolecarboxylic acid ethylamide; geldanamycin; chaperone; myeloid leukemia; drug solubility; clinical trial (topic); gastrointestinal tumor; snx 5422; focal epilepsy; pu h 71; at 13387; cnf 2024; cudc 305; kw 2478; pu 3; retaspimycin; crizotinib; heart atrium flutter; uremia; 17 desmethoxy 17 amino geldanamycin; ds 2248; ganetespib; ipi 493; mpc 3100; pu h 74; xl 888; night blindness |
| Journal Title: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research |
| Volume: | 1823 |
| Issue: | 3 |
| ISSN: | 0167-4889 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2012-03-01 |
| Start Page: | 742 |
| End Page: | 755 |
| Language: | English |
| DOI: | 10.1016/j.bbamcr.2011.10.008 |
| PROVIDER: | scopus |
| PMCID: | PMC3288123 |
| PUBMED: | 22062686 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "CODEN: BAMRD" - "Source: Scopus" |
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