PIM Kinase as an Executional Target in Cancer
PIM (proviral integration site for moloney murine leukemia virus) kinase plays a vital role being an oncogene in a variety of cancers including myeloma, leukemia, prostate and breast cancers. The aberrant expression and/or activation of PIM kinases in a variety of 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, correspondingly. All PIM kinases cause transcriptional activation of genes involved with cell survival and cell cycle progression in cancer. A number of pro-tumorigenic signaling molecules, for example MYC, p21Cip1/Waf1/p27kip1, CDC25, Notch1 and BAD have being best known as the downstream targets of PIM kinases. To date, three types of adenosine triphosphate-competitive PIM inhibitors, SGI-1776, AZD1208, and LGH447 will be in numerous studies to treat acute myelogenous leukemia, cancer of the prostate, lymphoma, or multiple myeloma. This review sheds light around the signaling pathways active in the PIM kinase regulation and current status of developing PIM kinase inhibitors as clinical success in combating human cancer.