Molecular Cancer volume 22 , Article number: 18 Cite this article. Metrics details. Decades of research has recognized a solid role for Pim kinases in lymphoproliferative disorders.
Targeting Pim kinases represents an interesting approach since knock-down of Pim kinases leads to non-fatal phenotypes in vivo suggesting clinical inhibition of Pim may have less side effects. In addition, the ATP binding site offers unique characteristics that can be used for the development of small inhibitors targeting one or all Pim isoforms. This review takes a closer look at Pim kinase expression and involvement in hematopoietic cancers.
Current and past clinical trials and in vitro characterization of Pim kinase inhibitors are examined and future directions are discussed. Current studies suggest that Pim kinase inhibition may be most valuable when accompanied by multi-drug targeting therapy. Early studies of the original Pim kinase, Pim-1, led to the discovery of an oncogenic role for the Pim kinase family in lymphoma [ 1 , 2 ].
A third member of the family, Pim-3, was found to catalyze histone phosphorylation and autophosphorylation [ 4 ]. All three Pim proteins can phosphorylate serine and threonine amino acids [ 5 ]; and can activate similar cellular pathways.
This has led researchers to believe that individual Pim kinases are compensatory, whereby the loss of one Pim kinase can be alleviated by the expression of another Pim kinase. There are several counterpoints to this theory, since individual Pim kinases have different expression patterns in cancer s , distinct tissue locations, dissimilar regulation, and are encoded on different chromosomes [ 6 ].
