Atalay Pinar, Ozpolat Bulent
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
Methodist Neil Cancer Center, Houston, TX 77030, USA.
Cancers (Basel). 2024 Jan 26;16(3):535. doi: 10.3390/cancers16030535.
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（莫洛尼病毒整合位点3原病毒）是一种丝氨酸/苏氨酸激酶，属于PIM家族（PIM1、PIM2和PIM3）。PIM3是一种原癌基因，在源自内胚层衍生组织的癌症中经常过度表达，如肝癌、胰腺癌、结肠癌、胃癌、前列腺癌和乳腺癌。PIM3在激活多种致癌信号通路中起关键作用，促进癌细胞增殖、存活、侵袭、肿瘤生长、转移和进展，以及化疗和放疗抗性和免疫抑制微环境。对PIM3表达的基因抑制可抑制实体癌小鼠的体外细胞增殖和体内肿瘤生长及转移，表明PIM3是一个潜在的治疗靶点。尽管几种泛PIM抑制剂已进入血液系统癌症的I期临床试验，但目前尚无FDA批准的用于治疗患者的抑制剂。本综述概述了PIM3在各种癌症中的作用及其作为癌症治疗新分子靶点的潜力的最新进展和见解。我们还讨论了PIM靶向治疗在临床试验中的现状。
