title: Exploiting the cytoskeletal filaments of neoplastic cells to potentiate a novel therapeutic approach.
abstract: Although cytoskeletal-directed agents have been a mainstay in chemotherapeutic protocols due to their ability to readily interfere with the rapid mitotic progression of neoplastic cells, they are all microtubule-based drugs, and there has yet to be any microfilament- or intermediate filament-directed agents approved for clinical use. There are many inherent differences between the cytoskeletal networks of malignant and normal cells, providing an ideal target to attain preferential damage. Further, numerous microfilament-directed agents, and an intermediate filament-directed agent of particular interest (withaferin A) have demonstrated in vitro and in vivo efficacy, suggesting that cytoskeletal filaments may be exploited to supplement chemotherapeutic approaches currently used in the clinical setting. Therefore, this review is intended to expose academics and clinicians to the tremendous variety of cytoskeletal filament-directed agents that are currently available for further chemotherapeutic evaluation. The mechanisms by which microfilament directed- and intermediate filament-directed agents damage malignant cells are discussed in detail in order to establish how the drugs can be used in combination with each other, or with currently approved chemotherapeutic agents to generate a substantial synergistic attack, potentially establishing a new paradigm of chemotherapeutic agents.
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA. Electronic address: mrtrendo@syr.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Trendowski
mesh_terms: D003572:Cytochalasins / Q000627:therapeutic use; D003599:Cytoskeleton / Q000187:drug effects*; D047630:Depsipeptides / Q000627:therapeutic use; D006801:Humans; D026121:Indole Alkaloids / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D019311:Staurosporine / Q000627:therapeutic use
chemical_list: D003572:Cytochalasins; D047630:Depsipeptides; D026121:Indole Alkaloids; C057531:jasplakinolide; C019290:chaetoglobosins; D019311:Staurosporine
keywords: Actin; Chemotherapy; Drug synergy; Intermediate filaments; Microfilaments