Multiple modes of action of eribulin mesylate: Emerging data and clinical implications
| Autor: | Bruce A. Littlefield, Javier Cortes, Patrick Schöffski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Eribulin Mesylate Epithelial-Mesenchymal Transition PACLITAXEL Microtubules Microtubule polymerization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Antimitotic In vivo Neoplasms PRECLINICAL ANTITUMOR-ACTIVITY BINDING medicine Humans Radiology Nuclear Medicine and imaging Epithelial–mesenchymal transition Eribulin Furans HALICHONDRIN-B Tumor microenvironment Science & Technology Neovascularization Pathologic business.industry EMT Cancer General Medicine Ketones medicine.disease Metastatic breast cancer EPITHELIAL-MESENCHYMAL TRANSITION CANCER 030104 developmental biology chemistry Oncology Epithelial-to-mesenchymal transition HOMOHALICHONDRIN-B Survival benefit 030220 oncology & carcinogenesis METASTASIS Cancer research business Life Sciences & Biomedicine |
| Popis: | Eribulin mesylate (eribulin) is a synthetic analogue of the marine-sponge natural product halichondrin B. Eribulin exhibits potent antiproliferative activities against a variety of human cancer cell types in vitro and in vivo, and is used for the treatment of certain patients with advanced breast cancer or liposarcoma who are refractory to other treatments. The antiproliferative effects of eribulin have long been attributed to its antimitotic activities. Unlike other microtubule-targeting agents, eribulin inhibits microtubule polymerization through specific plus end binding, thus interfering with microtubule dynamic instability. Non-mitotic effects of eribulin on tumor biology have also been established in laboratory settings including: tumor vasculature remodeling, increased vascular perfusion, reduced hypoxia, and phenotypic changes involving reversal of epithelial-to-mesenchymal transition (EMT), resulting in reduced capacities for migration, invasion, and seeding lung metastases in experimental models. Preclinical data suggest that increased perfusion following eribulin treatment improves delivery of subsequent drugs. Supporting evidence for eribulin's non-mitotic effects in the clinical setting include increased tumor oxygen saturation, reduced hypoxia, phenotype changes consistent with EMT reversal, and genotype changes consistent with shifts from nonendocrine-responsive, luminal B, to endocrine-responsive, luminal A, breast cancer subtypes. Finally, potential biomarkers for eribulin response have been established based on tumor-phenotype and gene-expression profiles. Overall, preclinical and clinical data support both antimitotic and non-mitotic mechanisms of eribulin that may underlie the survival benefit observed in various clinical trials. ispartof: CANCER TREATMENT REVIEWS vol:70 pages:190-198 ispartof: location:Netherlands status: published |
| Databáze: | OpenAIRE |
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