HSP90 inhibitors for cancer therapy and overcoming drug resistance Journal Article


Authors: Jhaveri, K.; Modi, S.
Article Title: HSP90 inhibitors for cancer therapy and overcoming drug resistance
Abstract: Since the initial discovery of heat shock protein 90 (HSP90) as a target for anticancer therapy, tremendous progress has been made in developing a multitude of potent first- and second-generation HSP90 inhibitors. Promising activity has been reported with 17-AAG in combination with trastuzumab in HER2 positive breast cancer refractory to trastuzumab therapy and more recently in ALK-mutated lung cancers. However, the full potential of this class of agents is yet to be realized. This review not only provides an up-to-date overview of the clinical development of HSP90 inhibitors and their companion biomarker assays but also provides insight into the less-understood role of HSP90 in tumor evolution and drug resistance. A better understanding of these important concepts will facilitate the optimal and expedient development of this class of agents, ultimately fulfilling their promise as potent anticancer therapeutics and leading to the regulatory approval of the first-in-class HSP90 inhibitor. © 2012 Elsevier Inc.
Keywords: treatment response; leukemia; unclassified drug; fatigue; cisplatin; cancer combination chemotherapy; drug efficacy; drug potentiation; drug safety; monotherapy; nonhuman; antineoplastic agents; clinical trials as topic; drug targeting; gemcitabine; cytarabine; protein function; neoplasms; biomarkers; biological marker; animals; diagnostic procedure; melanoma; breast cancer; kidney disease; lung non small cell cancer; thrombocytopenia; peripheral neuropathy; tumor markers, biological; lung cancer; kidney failure; tumor biopsy; antineoplastic activity; cytotoxicity; drug structure; drug resistance; drug resistance, neoplasm; drug development; cancer therapy; carcinogenesis; docetaxel; irinotecan; pneumonia; prostate cancer; drug fatality; hypotension; heat shock protein 90 inhibitor; pu h71; tanespimycin; heat shock protein 90; hsp90 heat-shock proteins; purine derivative; drug blood level; kidney cancer; trastuzumab; dry eye; chondrosarcoma; pharmacokinetics; blurred vision; keratitis; purine; 5 (2,4 dihydroxy 5 isopropylphenyl) 4 (4 morpholinomethylphenyl) 3 isoxazolecarboxylic acid ethylamide; geldanamycin; hsp90; snx 5422; alvespimycin; at 13387; cnf 2024; cudc 305; kw 2478; retaspimycin; resorcinol; biib 021; acidosis; client proteins; ds 2248; ganetespib; ipi 493; mpc 3100; xl 888; estrogen receptor positive breast cancer; pharmacodynamic assays; hsp 990; ver 52269; castrate refractory prostate cancer
Journal Title: Advances in Pharmacology
Volume: 65
ISSN: 1054-3589
Publisher: Elsevier Inc.  
Date Published: 2012-01-01
Start Page: 471
End Page: 517
Language: English
DOI: 10.1016/b978-0-12-397927-8.00015-4
PROVIDER: scopus
PUBMED: 22959035
DOI/URL:
Notes: --- Book Chapter 15 in "Current Challenges in Personalized Cancer Medicine" (ISBN: 978-0-12-397927-8) - "Export Date: 1 October 2012" - "Source: Scopus"
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MSK Authors
  1. Shanu Modi
    148 Modi
  2. Komal Lachhman Jhaveri
    54 Jhaveri