Journal article
Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current pharmaceutical design, v 18(19), pp 2778-2792
01 Jun 2012
PMID: 22390762
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tubulin is the target of some of the most widely used and time-honored anticancer tubulin-binding agents (TBAs). The clinical usefulness of many TBAs has been held back as a result of tumor cell drug-resistance. The elucidation of the three-dimensional structure of alpha beta-tubulin dimer has provided an opportunity for rational drug design aimed at generating compounds that will target tubulin in therapeutically more efficacious ways compared to presently available drugs. An issue to be addressed is which one(s) of the tubulin species, their isotypes, or their posttranslationally modified forms, should be specifically targeted in cancer chemotherapy. This review offers a critical appraisal of current knowledge on tubulins in cancer and an update on new anti-neoplastic microtubule-targeted treatment strategies. Specifically, it examines, across disciplines, cellular/molecular, biochemical, clinical/pathological, and pharmacological aspects of beta-tubulin isotypes, posttranslational modifications of tubulin dimers, gamma-tubulin and microtubule nucleation, and microtubule regulatory proteins. Emphasis is placed on the overexpression of (i) the beta III isotype, which functions as a survival factor associated with dynamic instability of microtubules; (ii) gamma-tubulin, a key microtubule nucleating protein; and (iii) the microtubule severing enzyme spastin, involved in cell motility and proliferation of glioblastoma cells. The role of III-tubulin in resistance of cancer cells to taxanes is examined. Attention is called to the novel concept that III-tubulin functions as a "gateway" for prosurvival signals in partnership with GTPases, such as GBP1. Appraisal is also offered on epothilones and the concept of hypersensitization to TBAs as promising therapeutic strategies in taxane resistant epithelial cancers and in high-grade gliomas.
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Details
- Title
- Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
- Creators
- Christos D. Katsetos - St. Christopher's Hospital for ChildrenPavel Draber - Cytoskeleton (United States)
- Publication Details
- Current pharmaceutical design, v 18(19), pp 2778-2792
- Publisher
- Bentham Science Publ Ltd
- Number of pages
- 15
- Grant note
- 1M6837805001 / Ministry of Education, Youth and Sports of the Czech Republic; Ministry of Education, Youth & Sports - Czech Republic 203 / St. Christopher's Foundation for Children 204/09/1777; KAN200520701 / Grant Agency of the Czech Republic
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000306546900010
- Scopus ID
- 2-s2.0-84862580438
- Other Identifier
- 991019353630504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pharmacology & Pharmacy