Feneyrolles Clémence, Spenlinhauer Aurélia, Guiet Léa, Fauvel Bénédicte, Daydé-Cazals Bénédicte, Warnault Pierre, Chevé Gwénaël, Yasri Aziz
OriBase Pharma, Cap Gamma, Montpellier, France.
OriBase Pharma, Cap Gamma, Montpellier, France
Mol Cancer Ther. 2014 Sep;13(9):2141-8. doi: 10.1158/1535-7163.MCT-13-1083. Epub 2014 Aug 19.
Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily, Axl regulates key processes such as cell growth, migration, aggregation, and apoptosis through several pathways. Its overexpression/overactivation has been underlined in several conditions, especially cancers, and in both chemotherapy and targeted therapy sensitivity loss. In this review, we propose to highlight the therapeutic implication of Axl, starting with the pathways it regulates, validating its interest as a therapeutic target, and defining the tools available to develop strategies for its inhibition. We especially focus on small molecule inhibitors, their structure, inhibition profile, and development stages.
受体酪氨酸激酶(RTK)是调节细胞内信号转导的跨膜受体。作为TAM(Tyro-3、Axl、Mer)RTK亚家族的成员,Axl通过多种途径调节细胞生长、迁移、聚集和凋亡等关键过程。在多种情况下,尤其是癌症以及化疗和靶向治疗敏感性丧失中,其过表达/过度激活已得到强调。在本综述中,我们建议突出Axl的治疗意义,首先介绍它所调节的途径,验证其作为治疗靶点的价值,并确定可用于开发其抑制策略的工具。我们特别关注小分子抑制剂,包括它们的结构、抑制谱和开发阶段。