PIM3 (provirus-integrating Moloney site 3) is a serine/threonine kinase and belongs to the PIM family (PIM1, PIM2, and PIM3). PIM3 is a proto-oncogene that is frequently overexpressed in cancers originating from endoderm-derived tissues, such as the liver, pancreas, colon, stomach, prostate, and breast cancer. PIM3 plays a critical role in activating multiple oncogenic signaling pathways promoting cancer cell proliferation, survival, invasion, tumor growth, metastasis, and progression, as well as chemo- and radiation therapy resistance and immunosuppressive microenvironment. Genetic inhibition of PIM3 expression suppresses in vitro cell proliferation and in vivo tumor growth and metastasis in mice with solid cancers, indicating that PIM3 is a potential therapeutic target. Although several pan-PIM inhibitors entered phase I clinical trials in hematological cancers, there are currently no FDA-approved inhibitors for the treatment of patients. This review provides an overview of recent developments and insights into the role of PIM3 in various cancers and its potential as a novel molecular target for cancer therapy. We also discuss the current status of PIM-targeted therapies in clinical trials.
PIM3（前病毒整合莫洛尼位点3）是一种丝氨酸/苏氨酸激酶，属于PIM家族（包括PIM1、PIM2和PIM3）。作为原癌基因，PIM3在内胚层来源组织（如肝脏、胰腺、结肠、胃、前列腺及乳腺）的癌症中常出现过表达。该基因通过激活多种致癌信号通路，在促进癌细胞增殖、存活、侵袭、肿瘤生长、转移及进展中发挥关键作用，同时与放化疗耐药及免疫抑制微环境的形成密切相关。遗传学抑制PIM3表达可显著抑制实体瘤小鼠模型的体外细胞增殖和体内肿瘤生长与转移，表明PIM3是具有潜力的治疗靶点。尽管已有数种泛PIM抑制剂进入血液系统恶性肿瘤的I期临床试验，但目前尚无获得FDA批准用于临床治疗的PIM抑制剂。本综述系统阐述了PIM3在不同癌症中的作用机制研究进展，探讨其作为新型癌症治疗分子靶点的潜力，并对当前靶向PIM的临床试验现状进行评述。
肿瘤(癌症)患者之家