von Itzstein Mitchell S, Burke Michael C, Brekken Rolf A, Aguilera Todd A, Zeh Herbert J, Beg Muhammad Shaalan
Division of Hematology/Oncology, Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA.
Division of Hematology and Medical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Target Oncol. 2020 Oct;15(5):579-588. doi: 10.1007/s11523-020-00751-9.
Pancreatic cancer is expected to become the second leading cause of cancer-related death within the next few years. Current therapeutic strategies have limited effectiveness and therefore there is an urgency to develop novel effective therapies. The receptor tyrosine kinase subfamily TAM (Tyro3, Axl, MerTK) is directly implicated in the pathogenesis of the metastatic, chemoresistant, and immunosuppressive phenotype in pancreatic cancer. TAM inhibitors are promising investigational therapies for pancreatic cancer due to their potential to target multiple aspects of pancreatic cancer biology. Specifically, recent mechanistic investigations and therapeutic combinations in the preclinical setting suggest that TAM inhibition with chemotherapy, targeted therapy, and immunotherapy should be evaluated clinically.
预计在未来几年内,胰腺癌将成为癌症相关死亡的第二大主要原因。目前的治疗策略效果有限,因此迫切需要开发新的有效疗法。受体酪氨酸激酶亚家族TAM(Tyro3、Axl、MerTK)直接参与胰腺癌转移、化疗耐药和免疫抑制表型的发病机制。TAM抑制剂有望成为胰腺癌的研究性治疗方法,因为它们有可能针对胰腺癌生物学的多个方面。具体而言,最近在临床前环境中的机制研究和治疗组合表明,应在临床上评估TAM抑制与化疗、靶向治疗和免疫治疗的联合应用。