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- Title
PIM3 Kinase: A Promising Novel Target in Solid Cancers.
- Authors
Atalay, Pinar; Ozpolat, Bulent
- Abstract
Simple Summary: PIM3 is a serine/threonine kinase linked to various oncogenic processes and often overexpressed in solid cancers such as pancreatic, liver, colon, stomach, and breast cancers. Upregulation of PIM3 is associated with poor patient prognosis, and its inhibition leads to reduced cell proliferation, invasion, and in vivo tumor growth; thus, PIM3 represents an emerging novel therapeutic target in cancer. Although pan-PIM inhibitors have entered clinical trials in hematological cancers, they were not potent or specific enough or exhibited side effects; thus, currently, there is no FDA-approved inhibitor for targeting all PIMs or PIM3. The development of selective and effective PIM3 inhibitors may have a significant clinical impact and a novel potential therapeutic strategy for PIM3-driven solid and hematological cancers. 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.
- Subjects
TUMOR treatment; SURVIVAL; DISEASE progression; IN vitro studies; IN vivo studies; THREONINE; PROTEIN kinase inhibitors; CARCINOGENESIS; CANCER invasiveness; CANCER chemotherapy; METASTASIS; IMMUNOSUPPRESSION; CELLULAR signal transduction; GENE expression; SERINE; CELL proliferation; RADIOTHERAPY; DRUG resistance in cancer cells
- Publication
Cancers, 2024, Vol 16, Issue 3, p535
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16030535