title: Epothilones in development for non--small-cell lung cancer: novel anti-tubulin agents with the potential to overcome taxane resistance.
abstract: Progress in the treatment of non-small-cell lung cancer (NSCLC) will require the introduction of new agents as well as better use of existing therapies. Targeted therapies are likely to have a profound effect on the treatment of NSCLC after identification of patients who are most likely to benefit. The epothilones are novel anti-tubulin agents derived from Sorangium cellulosum. β III tubulin overexpression has been implicated as a mechanism of anti-tubulin resistance that can be overcome by epothilones. Several epothilones have advanced to clinical trials; ixabepilone (BMS247550, aza-epothilone B, Bristol-Myers Squibb, New York, NY), patupilone (EPO906, Novartis, Basel, Switzerland) and sagopilone (ZK-EPO, ZK-219477, Schering AG, Berlin-Wedding, Germany) are currently in active development. Several of the epothilones, most notably ixabepilone, have demonstrated activity in lung cancer in phase I and II trials, including taxane-resistant patients. Although a phase II study failed to show superior outcome in patients with β III tubulin overexpression, other aspects of the epothilones argue for their continued development.
authors: University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA. medelman@umm.edu
authors: Martin J
authors: MJ
authors: Edelman
authors: Marianna
authors: M
authors: Shvartsbeyn
mesh_terms: D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000627:therapeutic use*
chemical_list: D001952:Bridged-Ring Compounds; D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; C080625:taxane