PIM Kinase as an Executional Target in Cancer
10.15430/JCP.2018.23.3.109
- Author:
Xinning ZHANG
1
;
Mengqiu SONG
;
Joydeb Kumar KUNDU
;
Mee Hyun LEE
;
Zhen Zhen LIU
Author Information
1. Department of Breast Surgery, Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. liuzhenzhen73@163.com
- Publication Type:Review
- Keywords:
Proto-oncogene proteins PIM kinase;
PIM signaling pathways;
PIM kinase inhibitor
- MeSH:
Adenosine;
Breast;
Cell Cycle;
Cell Survival;
Humans;
Leukemia;
Leukemia, Myeloid, Acute;
Lymphoma;
Multiple Myeloma;
Oncogenes;
Phosphotransferases;
Prostate;
Prostatic Neoplasms;
Transcriptional Activation
- From:Journal of Cancer Prevention
2018;23(3):109-116
- CountryRepublic of Korea
- Language:English
-
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.
