Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas.
Methodist Neil Cancer Center, Houston, Texas.
Mol Cancer Ther. 2023 Jul 5;22(7):818-832. doi: 10.1158/1535-7163.MCT-22-0617.
Early cancer recurrence, driven by resistance to therapeutics, is a major obstacle to overcome poor survival in triple-negative breast cancer (TNBC). Recently, overexpression of AXL has been identified as one of the key molecular determinants leading to the development of acquired resistance to chemotherapy and targeted anticancer treatments. AXL overactivation drives many hallmarks of cancer progression, including cell proliferation, survival, migration, metastasis, drug resistance, and is linked to poor patient survival and disease recurrence. Mechanistically, AXL represents a signaling hub that regulates a complex signaling pathways crosstalk. Therefore, emerging data highlight the clinical significance of AXL as an attractive therapeutic target. Currently, there is no FDA approved AXL inhibitor but several AXL small molecule inhibitors and antibodies are being tested in clinical settings. In this review we outline the functions and regulation of AXL, its role in resistance to therapy, and current strategies targeting AXL with emphasis on TNBC.
早期癌症复发是三阴性乳腺癌（TNBC）患者生存率差的主要障碍，其主要由治疗耐药驱动。最近，AXL 的过表达被确定为导致化疗和靶向抗癌治疗获得性耐药的关键分子决定因素之一。AXL 的过度激活驱动着癌症进展的许多特征，包括细胞增殖、存活、迁移、转移、耐药性，并且与患者生存率差和疾病复发相关。从机制上讲，AXL 代表了一个信号枢纽，调节着复杂的信号通路串扰。因此，新出现的数据强调了 AXL 作为一个有吸引力的治疗靶点的临床意义。目前，还没有 FDA 批准的 AXL 抑制剂，但有几种 AXL 小分子抑制剂和抗体正在临床环境中进行测试。在这篇综述中，我们概述了 AXL 的功能和调节、它在耐药性中的作用以及目前针对 AXL 的策略，重点是 TNBC。
