From taxanes to epothilones: Targeting microtubules in breast cancer and beyond
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چکیده
Taxane re-treatment is complicated by: modest and variable efficacy to same5 or different taxane6 b f i d fi i i f “ i ” a sence o str ct e n t on o res stance uncertainty as to impact of disease-free / taxane-free interval on response rate 1NCCN Clinical Practice Guidelines in Oncology, Breast Cancer V.1.2009 2A d l & H t b i J Cli O l 2008 26 3660 2 n reopou ou or o agy , n nco ; : – 3Tan et al, Br J Cancer 2009; 100: 405–11 4Burns et al, ASCO Breast Cancer Symposium 2008; Abstract 139 5Seidman et al, J Clin Oncol 1996; 14: 1877–84 6Valero et al, J Clin Oncol 1998; 16: 3362–8 Slide 1
منابع مشابه
Novel microtubule-targeting agents – the epothilones
Epothilones are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from taxanes and are more amenable to synthetic modification. Six epothilones have been studied in preclinical and clinical trials: patupilone (epothilone B), ixabepilone (BMS247550), BMS 310705, sagopilone (ZK-EPO), KOS-862 (epothilone D), and KOS-1584. In vitro data have ...
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Microtubules are essential to cell transport, signaling, and mitosis. An increasing range of anticancer drugs interferes with the normal formation and function of microtubules. Vinca alkaloids act as microtubule destabilizers and the taxanes act as microtubule stabilizers. Taxanes are widely used cytotoxic agents that are active in a range of solid tumor malignancies and are routinely used in a...
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BACKGROUND Drugs that target microtubules, including paclitaxel (Taxol) and docetaxel (Taxotere), are among the most commonly prescribed anticancer therapies. However, the utility of taxane-based therapies is limited by difficulties with formulation, administration, and resistance induced by P-glycoprotein. The epothilones are a novel class of antimicrotubule agents that have demonstrated antit...
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The epothilones are macrolide compounds that have been shown to stabilize microtubules. The epothilones are strong promoters of tubulin polymerization in vitro and have significant antitumor activity against human cancer cells that are taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have acquired tubulin mutations. Several epothilones have been evaluated in clinical t...
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The dynamic balance between microtubule extension and actin contraction regulates mammalian cell shape, division, and motility, which has made the cytoskeleton an attractive and very successful target for cancer drugs. Numerous compounds in clinical use to reduce tumor growth cause microtubule breakdown (vinca alkaloids, colchicine-site, and halichondrins) or hyperstabilization of microtubules ...
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