Risinger April L, Giles Francis J, Mooberry Susan L
Department of Pharmacology, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Cancer Treat Rev. 2009 May;35(3):255-61. doi: 10.1016/j.ctrv.2008.11.001. Epub 2008 Dec 30.
Drugs that affect microtubule dynamics, including the taxanes and vinca alkaloids, have been a mainstay in the treatment of leukemias and solid tumors for decades. New, more effective microtubule-targeting agents continue to enter into clinical trials and some, including the epothilone ixapebilone, have been approved for use. In contrast, several other drugs of this class with promising preclinical data were later shown to be ineffective or intolerable in animal models or clinical trials. In this review, we discuss the molecular mechanisms as well as preclinical and clinical results for a variety of microtubule-targeting agents in various stages of development. We also offer a frank discussion of which microtubule-targeting agents are amenable to further development based on their availability, efficacy and toxic profile.
数十年来,影响微管动力学的药物,包括紫杉烷类和长春花生物碱,一直是白血病和实体瘤治疗的中流砥柱。新型、更有效的微管靶向药物不断进入临床试验,其中一些药物,包括埃坡霉素伊沙匹隆,已获批使用。相比之下,这类其他几种在临床前数据很有前景的药物,后来在动物模型或临床试验中被证明无效或无法耐受。在本综述中,我们讨论了处于不同开发阶段的各种微管靶向药物的分子机制以及临床前和临床结果。我们还坦率地讨论了哪些微管靶向药物基于其可得性、疗效和毒性特征适合进一步开发。