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PIM Kinase as an Executional Target in Cancer
Journal of Cancer Prevention 2018;23:109-16
Published online September 30, 2018
© 2018 Korean Society of Cancer Prevention.

Xinning Zhang1,*, Mengqiu Song2,3,*, Joydeb Kumar Kundu4, Mee-Hyun Lee2,3, Zhen-Zhen Liu1

1Department of Breast Surgery, Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,2Basic Medical College, Zhengzhou University,3China-US (Henan) Hormel Cancer Institute, Zhengzhou, China, 4Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada
Correspondence to: Zhen-Zhen Liu
Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, China
Tel: +86-136-0386-2755, Fax: +86-371-65588134, E-mail: liuzhenzhen73@163.com, ORCID: Zhen-Zhen Liu, https://orcid.org/0000-XYZQ-ABCD-EFGH
Correspondence to: Mee-Hyun Lee
China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, Henan, 450008, China
Tel: +86-371-65587008, Fax: +86-371-65587670, E-mail: mhlee@hci-cn.org, ORCID: Mee-Hyun Lee, https://orcid.org/0000-0002-5141-1112
*These authors contributed equally to this work as co-first authors.
Received April 4, 2018; Revised April 25, 2018; Accepted April 30, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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, p21Cip1/Waf1/p27kip1, 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.
Keywords : Proto-oncogene proteins PIM kinase, PIM signaling pathways, PIM kinase inhibitor


September 2018, 23 (3)
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