Tripathi Rakshamani, Liu Zulong, Plattner Rina
Department of Pharmacology and Nutritional Sciences, University of Kentucky School of Medicine, Lexington, Kentucky 40536.
Curr Pharmacol Rep. 2018 Oct;4(5):367-379. doi: 10.1007/s40495-018-0149-y. Epub 2018 Jul 23.
The goal of this review is to summarize our current knowledge regarding how ABL family kinases are activated in solid tumors and impact on solid tumor development/progression, with a focus on recent advances in the field.
Although ABL kinases are known drivers of human leukemia, emerging data also implicates the kinases in a large number of solid tumor types where they promote diverse processes such as proliferation, survival, cytoskeletal reorganization, cellular polarity, EMT (epithelial-mesenchymal-transition), metabolic reprogramming, migration, invasion and metastasis via unique signaling pathways. ABL1 and ABL2 appear to have overlapping but also unique roles in driving these processes. In some tumor types, the kinases may act to integrate pro- and anti-proliferative and -invasive signals, and also may serve as a switch during EMT/MET (mesenchymal-epithelial) transitions.
Most data indicate that targeting ABL kinases may be effective for reducing tumor growth and preventing metastasis; however, ABL kinases also may have a tumor suppressive role in some tumor types and in some cellular contexts. Understanding the functions of ABL kinases in solid tumors is critical for developing successful clinical trials aimed at targeting ABL kinases for the treatment of solid tumors.
本综述旨在总结我们目前关于ABL家族激酶在实体瘤中如何被激活以及对实体瘤发展/进展的影响的知识，重点关注该领域的最新进展。
尽管ABL激酶是人类白血病的已知驱动因素，但新出现的数据也表明这些激酶在大量实体瘤类型中发挥作用，它们通过独特的信号通路促进多种过程，如增殖、存活、细胞骨架重组、细胞极性、上皮-间质转化（EMT）、代谢重编程、迁移、侵袭和转移。ABL1和ABL2在驱动这些过程中似乎具有重叠但也独特的作用。在某些肿瘤类型中，这些激酶可能起到整合促增殖和抗增殖以及侵袭信号的作用，并且在EMT/间质-上皮转化（MET）过程中也可能充当开关。
大多数数据表明，靶向ABL激酶可能对减少肿瘤生长和预防转移有效；然而，ABL激酶在某些肿瘤类型和某些细胞环境中也可能具有肿瘤抑制作用。了解ABL激酶在实体瘤中的功能对于开展旨在靶向ABL激酶治疗实体瘤的成功临床试验至关重要。
