Winthrop University Hospital, Mineola, NY, USA.
Cancer J. 2013 Jan-Feb;19(1):59-65. doi: 10.1097/PPO.0b013e3182828d38.
Microtubules are dynamic filamentous cytoskeletal proteins that are responsible for cellular integrity and architecture, mitosis, intracellular transport, cell signaling, and gene expression. Tubulin exists in the cell as dimers of α and β subunits, which complexes with a variety of regulatory proteins. There is a dynamic equilibrium between free and polymerized tubulin causing a state called "dynamic instability," which is a target of anticancer drugs, which inhibit tubulin through polymerization (taxanes, epothilones) or depolymerization (vinca alkaloids). Docetaxel-based therapy was the first such treatment to demonstrate a survival benefit in men with castration-resistant prostate cancer. Cabazitaxel, an antitubulin agent, which demonstrates activity in multidrug- and docetaxel-resistant cancer cell lines, demonstrates a survival benefit over mitoxantrone and prednisone in patients who have failed docetaxel-based chemotherapy. This article reviews the use of antitubulin agents in patients with castration-resistant prostate cancer.
微管是一种动态的丝状细胞骨架蛋白，负责细胞的完整性和结构、有丝分裂、细胞内运输、细胞信号转导和基因表达。微管在细胞中以α和β亚基的二聚体形式存在，与各种调节蛋白复合物。游离态和聚合态的微管之间存在动态平衡，导致一种称为“动态不稳定性”的状态，这是抗癌药物的靶点，抗癌药物通过聚合（紫杉烷类、埃坡霉素类）或解聚（长春花生物碱）来抑制微管。基于多西紫杉醇的治疗是第一种在去势抵抗性前列腺癌男性中显示生存获益的治疗方法。卡巴他赛是一种抗微管药物，在多药耐药和多西紫杉醇耐药的癌细胞系中具有活性，在接受多西紫杉醇化疗失败的患者中，与米托蒽醌和泼尼松相比，具有生存获益。本文综述了抗微管药物在去势抵抗性前列腺癌患者中的应用。
