Hardin C, Shum E, Singh A P, Perez-Soler R, Cheng H
a Department of Medical Oncology , Albert Einstein College of Medicine/Montefiore Medical Center , Bronx , NY , USA.
Expert Opin Pharmacother. 2017 May;18(7):701-716. doi: 10.1080/14656566.2017.1316374. Epub 2017 Apr 17.
Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management. Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored. Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.
包括紫杉烷类和长春花生物碱在内的微管蛋白抑制剂是晚期非小细胞肺癌（NSCLC）化疗方案的重要组成部分。尽管由于分子靶向治疗和免疫治疗导致了治疗模式的转变，但大多数患者在其治疗过程中仍将接受化疗。无论单独使用还是联合使用，微管蛋白抑制剂在肺癌治疗的不同情况下均已显示出临床益处。涵盖领域：本综述首先讨论了美国食品药品监督管理局（FDA）批准的用于NSCLC的微管蛋白抑制剂，如紫杉醇、多西他赛、长春瑞滨和纳米白蛋白结合型紫杉醇。然后文章总结了新型微管蛋白抑制剂，包括卡巴他赛、艾瑞布林、伊沙匹隆、帕妥珠利、普利纳布林、新型秋水仙碱类似物等。还讨论了微管蛋白抑制剂与免疫治疗（PD-1/PD-L1抑制剂）和分子靶向治疗（如抗血管生成药物、mTOR抑制剂、热休克蛋白90抑制剂、MEK抑制剂和抗HER3药物）的新联合用药。最后，探讨了关于微管蛋白抑制剂潜在耐药机制和预测生物标志物的新数据。专家观点：由于新型药物和联合用药的出现，微管蛋白抑制剂可能会继续在NSCLC治疗中发挥重要作用。通过进一步了解肿瘤生物学、研究耐药性以及开发预测生物标志物，我们将更有能力将微管抑制纳入针对患者的具体治疗策略中。
