PIM Kinase as an Executional Target in Cancer

by Selleckchem | Jul 10 2023

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.

Comments:

PIM (proviral integration site for Moloney murine leukemia virus) kinase is a group of protein kinases that have been implicated as oncogenes in various types of cancer, including myeloma, leukemia, prostate cancer, and breast cancer. These kinases, which include PIM1, PIM2, and PIM3, play a crucial role in promoting cell survival and cell cycle progression in cancer cells.

The expression and activation of PIM kinases in different cancers follow an isoform-specific pattern. PIM1 is predominantly expressed in both hematological malignancies and solid tumors. On the other hand, PIM2 is largely expressed in leukemia, while PIM3 is primarily found in solid tumors.

PIM kinases exert their oncogenic effects by promoting the transcriptional activation of genes involved in cell survival and cell cycle progression. Several downstream targets of PIM kinases have been identified, including MYC, p21Cip1/Waf1/p27kip1, CDC25, Notch1, and BAD. These molecules are involved in key signaling pathways that regulate cell proliferation, apoptosis, and differentiation.

In light of the role of PIM kinases in cancer, efforts have been made to develop PIM kinase inhibitors as potential therapeutics. Currently, three ATP-competitive PIM inhibitors, namely SGI-1776, AZD1208, and LGH447, have been investigated in clinical trials for the treatment of acute myelogenous leukemia, prostate cancer, lymphoma, and multiple myeloma. These inhibitors aim to block the activity of PIM kinases and thereby inhibit their downstream signaling pathways.

The development of PIM kinase inhibitors represents a promising approach in combating human cancer. Ongoing research and clinical trials will further elucidate the efficacy and safety of these inhibitors and their potential as targeted therapies for specific cancer types.