Dumontet Charles
Hospices civils de Lyon, université Lyon-I, centre de recherche en cancérologie de Lyon, France.
Bull Cancer. 2011 Nov;98(11):1275-85. doi: 10.1684/bdc.2011.1469.
Microtubules are dynamic filamentous cytoskeletal proteins that are an important therapeutic target in patients with tumors. Microtubule binding agents have been part of the pharmacopoeia of cancer for decades, and until the advent of targeted therapy microtubules represented the only alternative to DNA as a therapeutic target in cancer. There are currently a variety of available vinca alkaloids and taxanes and other agents, such as ixabepilone and eribulin, have also been approved. Maytansinoids have been used for the production of immunoconjugates, monoclonal antibodies covalently bound to antimitotic molecules. The screening of a variety of botanical species and marine organisms continues to yield promising new antitubulin agents with novel properties. Enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms are the three main objectives in the current search for novel microtubule binding agents.
微管是动态的丝状细胞骨架蛋白,是肿瘤患者重要的治疗靶点。微管结合剂几十年来一直是癌症药典的一部分,在靶向治疗出现之前,微管是癌症治疗中除DNA之外唯一的治疗靶点。目前有多种可用的长春花生物碱和紫杉烷,其他药物如伊沙匹隆和艾瑞布林也已获批。美登素类已用于生产免疫缀合物,即与抗有丝分裂分子共价结合的单克隆抗体。对多种植物物种和海洋生物的筛选不断产生具有新特性的有前景的新型抗微管蛋白药物。提高肿瘤特异性、降低神经毒性以及对化疗耐药机制不敏感是当前寻找新型微管结合剂的三个主要目标。