University of Arizona Cancer Center, Tucson, Arizona.
Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona.
Mol Cancer Ther. 2021 Jan;20(1):3-10. doi: 10.1158/1535-7163.MCT-20-0535. Epub 2020 Dec 10.
Cancer progression and the onset of therapeutic resistance are often the results of uncontrolled activation of survival kinases. The proviral integration for the Moloney murine leukemia virus (PIM) kinases are oncogenic serine/threonine kinases that regulate tumorigenesis by phosphorylating a wide range of substrates that control cellular metabolism, proliferation, and survival. Because of their broad impact on cellular processes that facilitate progression and metastasis in many cancer types, it has become clear that the activation of PIM kinases is a significant driver of resistance to various types of anticancer therapies. As a result, efforts to target PIM kinases for anticancer therapy have intensified in recent years. Clinical and preclinical studies indicate that pharmacologic inhibition of PIM has the potential to significantly improve the efficacy of standard and targeted therapies. This review focuses on the signaling pathways through which PIM kinases promote cancer progression and resistance to therapy, as well as highlights biological contexts and promising strategies to exploit PIM as a therapeutic target in cancer.
癌症的进展和治疗耐药的发生通常是由于生存激酶的失控激活。莫洛尼鼠白血病病毒（PIM）激酶的前病毒整合是致癌的丝氨酸/苏氨酸激酶，通过磷酸化广泛的控制细胞代谢、增殖和存活的底物来调节肿瘤发生。由于它们对促进多种癌症类型进展和转移的细胞过程有广泛的影响，因此，PIM 激酶的激活已成为对各种类型抗癌疗法产生耐药性的重要驱动因素。因此，近年来针对 PIM 激酶进行抗癌治疗的努力已经加强。临床和临床前研究表明，PIM 的药理抑制有可能显著提高标准和靶向治疗的疗效。这篇综述重点介绍了 PIM 激酶促进癌症进展和对治疗耐药的信号通路，并强调了利用 PIM 作为癌症治疗靶点的生物学背景和有前途的策略。
