Pasquier Eddy, André Nicolas, Braguer Diane
FRE-CNRS 2737, CISMET (Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral), University of Aix-Marseille, 27 bd Jean Moulin, 13005 Marseille, France.
Curr Cancer Drug Targets. 2007 Sep;7(6):566-81. doi: 10.2174/156800907781662266.
Anticancer agents that interfere with tubulin functions are widely used in the clinic and have a broad spectrum of activity against both haematological malignancies and solid tumours. These Microtubule-Targeting Agents (MTAs), such as the taxanes and Vinca alkaloids, bind to the beta subunit of alpha/beta tubulin and disrupt microtubule dynamics in tumour cells, ultimately leading to mitotic block and subsequent cell death. Recently, MTAs have received considerable interest as potential tumour-selective anti-angiogenic and vascular-disrupting agents. Angiogenesis is a keystone of tumour progression and metastasis and targeting the formation of new blood vessels within the tumour is therefore regarded as a promising strategy for cancer therapy. In this regard, conventional MTAs can be given on daily schedules at non-toxic doses (metronomic dosing) to disturb tumour angiogenesis. Some MTAs can also act as vascular-disrupting agents. After briefly reviewing the classical mechanisms involved in the anti-tumour action of MTAs, we will focus on the latest studies investigating the molecular and cellular processes underlying the anti-angiogenic and the vascular-disrupting properties of these agents. We will also review and discuss the potential clinical development and the limitations of MTAs used as tumour-specific anti-vascular molecules.
干扰微管蛋白功能的抗癌药物在临床上广泛应用，对血液系统恶性肿瘤和实体瘤均有广泛的活性谱。这些微管靶向药物（MTA），如紫杉烷类和长春花生物碱，与α/β微管蛋白的β亚基结合，破坏肿瘤细胞中的微管动力学，最终导致有丝分裂阻滞和随后的细胞死亡。最近，MTA作为潜在的肿瘤选择性抗血管生成和血管破坏剂受到了相当大的关注。血管生成是肿瘤进展和转移的关键因素，因此靶向肿瘤内新血管的形成被认为是一种有前途的癌症治疗策略。在这方面，传统的MTA可以以无毒剂量按日常给药方案（节拍式给药）给药，以干扰肿瘤血管生成。一些MTA还可以作为血管破坏剂。在简要回顾MTA抗肿瘤作用的经典机制后，我们将重点关注研究这些药物抗血管生成和血管破坏特性的分子和细胞过程的最新研究。我们还将回顾和讨论用作肿瘤特异性抗血管分子的MTA的潜在临床开发和局限性。
