Institute of Biomedical and Biomolecular Science, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.
Cancer Res. 2017 Jun 1;77(11):2775-2778. doi: 10.1158/0008-5472.CAN-16-2675. Epub 2017 May 19.
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy. As chemoresistance is the leading cause of cancer spread, progression, and mortality, there is an increasing need for understanding the mechanisms by which cancer cells can evade therapy-induced cell death. The TAM (Tyro3, Axl, Mer) subfamily of RTKs in particular feature in a variety of cancer types that have developed resistance to a broad range of therapeutic agents, including both targeted as well as conventional chemotherapeutics. This article reviews the roles of TAMs as tumor drivers and as mediators of chemoresistance, and the potential effectiveness of targeting them as part of therapeutic strategies to delay or combat resistance. .
受体酪氨酸激酶（RTK）是细胞生长、存活和分化等关键生物过程的主要调节因子，它们很早就被确立为原癌基因，其异常表达与许多癌症的肿瘤进展有关。因此，RTK 已成为小分子抑制剂选择性治疗的主要靶点。然而，尽管生存率有所提高，但现在很明显，用选择性抑制剂靶向 RTK 的效果只是暂时的，因为大多数患者最终对治疗产生耐药性。由于化疗耐药性是癌症扩散、进展和死亡的主要原因，因此越来越需要了解癌细胞逃避治疗诱导的细胞死亡的机制。TAM（Tyro3、Axl、Mer）受体酪氨酸激酶亚家族在多种癌症类型中特别突出，这些癌症对广泛的治疗药物产生了耐药性，包括靶向药物和传统化疗药物。本文综述了 TAMs 作为肿瘤驱动因子和化疗耐药性的介导因子的作用，以及作为治疗策略的一部分靶向它们以延迟或对抗耐药性的潜在有效性。
