J Cancer Prev.  2018 Sep;23(3):109-116. 10.15430/JCP.2018.23.3.109.

PIM Kinase as an Executional Target in Cancer

• Zhang X
• Song M
• Kundu JK
• Lee MH
• Liu ZZ

• KMID: 2425313
• DOI: http://doi.org/10.15430/JCP.2018.23.3.109

Abstract

PIM (proviral integration site for moloney murine leukemia virus) kinase plays a key role as an oncogene in various cancers including myeloma, leukemia, prostate and breast cancers. The aberrant expression and/or activation of PIM kinases in various cancers follow an isoform-specific pattern. While PIM1 is predominantly expressed in hematological and solid tumors, PIM2 and PIM3 are largely expressed in leukemia and solid tumors, respectively. All of PIM kinases cause transcriptional activation of genes involved in cell survival and cell cycle progression in cancer. A variety of pro-tumorigenic signaling molecules, such as MYC, p21(Cip1/Waf1)/p27(kip1), CDC25, Notch1 and BAD have been identified as the downstream targets of PIM kinases. So far, three kinds of adenosine triphosphate-competitive PIM inhibitors, SGI-1776, AZD1208, and LGH447 have been in clinical trials for the treatment of acute myelogenous leukemia, prostate cancer, lymphoma, or multiple myeloma. This review sheds light on the signaling pathways involved in the PIM kinase regulation and current status of developing PIM kinase inhibitors as clinical success in combating human cancer.

Keyword

Proto-oncogene proteins PIM kinase; PIM signaling pathways; PIM kinase inhibitor

MeSH Terms

Adenosine
Breast
Cell Cycle
Cell Survival
Humans
Leukemia
Leukemia, Myeloid, Acute
Lymphoma
Multiple Myeloma
Oncogenes
Phosphotransferases*
Prostate
Prostatic Neoplasms
Transcriptional Activation
Adenosine
Phosphotransferases