Ganetespib: Research and clinical development Journal Article
| Authors: | Jhaveri, K.; Modi, S. |
| Article Title: | Ganetespib: Research and clinical development |
| Abstract: | Under stressful conditions, the heat shock protein 90 (HSP90) molecular chaperone protects cellular proteins (client proteins) from degradation via the ubiquitin-proteasome pathway. HSP90 expression is upregulated in cancers, and this contributes to the malignant phenotype of increased proliferation and decreased apoptosis and maintenance of metastatic potential via conservation of its client proteins, including human epidermal growth factor receptor 2, anaplastic lymphoma kinase, androgen receptor, estrogen receptor, Akt, Raf-1, cell cycle proteins, and B-cell lymphoma 2 among others. Hence, inhibition of HSP90 leads to the simultaneous degradation of its many clients, thereby disrupting multiple oncogenic signaling cascades. This has sparked tremendous interest in the development of HSP90 inhibitors as an innovative anticancer strategy. Based on the wealth of compelling data from preclinical studies, a number of HSP90 inhibitors have entered into clinical testing. However, despite enormous promise and anticancer activity reported to date, none of the HSP90 inhibitors in development has been approved for cancer therapy, and the full potential of this class of agents is yet to be realized. This article provides a review on ganetespib, a small molecule HSP90 inhibitor that is currently under evaluation in a broad range of cancer types in combination with other therapeutic agents with the hope of further enhancing its efficacy and overcoming drug resistance. Based on our current understanding of the complex HSP90 machinery combined with the emerging data from these key clinical trials, ganetespib has the potential to be the first-in-class HSP90 inhibitor to be approved as a new anticancer therapy. © 2015 Jhaveri and Modi. |
| Keywords: | overall survival; fatigue; review; cisplatin; doxorubicin; cancer combination chemotherapy; diarrhea; dose response; drug efficacy; nonhuman; recommended drug dose; solid tumor; capecitabine; paclitaxel; cancer radiotherapy; outcome assessment; colorectal cancer; gastrointestinal stromal tumor; carboplatin; progression free survival; apoptosis; bortezomib; mantle cell lymphoma; multiple cycle treatment; multiple myeloma; ovary cancer; peritoneum cancer; breast cancer; qt prolongation; lung cancer; antineoplastic activity; drug structure; docetaxel; asthenia; drug dose escalation; drug hypersensitivity; sarcoma; hyponatremia; lung adenocarcinoma; drug research; adverse outcome; clinical evaluation; aflibercept; pleura mesothelioma; heat shock protein 90; hyperbilirubinemia; trastuzumab; breast metastasis; rectum cancer; transitional cell carcinoma; pemetrexed; gastrointestinal disease; rapamycin; drug protein binding; fulvestrant; small cell lung cancer; hsp90; non small cell lung cancer; uterine tube tumor; metastatic melanoma; phase 2 clinical trial (topic); metastatic colorectal cancer; phase 1 clinical trial (topic); hypertransaminasemia; gastrointestinal carcinoma; crizotinib; ganetespib; human |
| Journal Title: | OncoTargets and Therapy |
| Volume: | 8 |
| ISSN: | 1178-6930 |
| Publisher: | Dove Medical Press Ltd |
| Date Published: | 2015-07-01 |
| Start Page: | 1849 |
| End Page: | 1858 |
| Language: | English |
| DOI: | 10.2147/ott.s65804 |
| PROVIDER: | scopus |
| PMCID: | PMC4521669 |
| PUBMED: | 26244021 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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