癌细胞及肿瘤免疫微环境对当前抗癌疗法中的先天性与获得性耐药机制需要新的治疗方法。TAM（TYRO3、AXL和MERTK）家族受体酪氨酸激酶（RTKs）是一系列癌症潜在治疗靶点。在癌细胞中，TAM RTKs会激活信号通路，促进细胞存活、转移和对多种化疗药物和靶向药物的耐药性。TAM RTKs还在先天免疫细胞中发挥作用，参与抑制抗肿瘤免疫和促进对免疫检查点抑制剂的耐药性的各种机制。因此，TAM拮抗剂提供了通过抑制单一靶点的直接和免疫介导的治疗活性的前所未有的机会，并且在与其他癌症治疗方法联合使用时可能特别有效。为了利用这一潜力，已经设计了多种选择性靶向TAM RTKs的药物，其中许多药物目前已进入临床测试阶段。本综述为临床医生提供了TAM RTKs的基本指南，包括对癌细胞及肿瘤免疫微环境中治疗靶向TAM RTKs的合理性的概述，对TAM抑制剂在目前临床前和临床经验的描述，以及关于继续开发面向肿瘤学应用的TAM靶向药物的策略的展望。© 2023. Springer Nature Limited.

Novel treatment approaches are needed to overcome innate and acquired mechanisms of resistance to current anticancer therapies in cancer cells and the tumour immune microenvironment. The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) are potential therapeutic targets in a wide range of cancers. In cancer cells, TAM RTKs activate signalling pathways that promote cell survival, metastasis and resistance to a variety of chemotherapeutic agents and targeted therapies. TAM RTKs also function in innate immune cells, contributing to various mechanisms that suppress antitumour immunity and promote resistance to immune-checkpoint inhibitors. Therefore, TAM antagonists provide an unprecedented opportunity for both direct and immune-mediated therapeutic activity provided by inhibition of a single target, and are likely to be particularly effective when used in combination with other cancer therapies. To exploit this potential, a variety of agents have been designed to selectively target TAM RTKs, many of which have now entered clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians, including an overview of the rationale for therapeutic targeting of TAM RTKs in cancer cells and the tumour immune microenvironment, a description of the current preclinical and clinical experience with TAM inhibitors, and a perspective on strategies for continued development of TAM-targeted agents for oncology applications.© 2023. Springer Nature Limited.