Targeting PIM Kinases to Overcome Therapeutic Resistance in Cancer

Cancer progression and the onset of therapeutic resistance are often the results of uncontrolled activation of survival kinases. The proviral integration for the Moloney murine leukemia virus (PIM) kinases are oncogenic serine/threonine kinases that regulate tumorigenesis by phosphorylating a wide range of substrates that control cellular metabolism, proliferation, and survival. Because of their broad impact on cellular processes that facilitate progression and metastasis in many cancer types, it has become clear that the activation of PIM kinases is a significant driver of resistance to various types of anticancer therapies. As a result, efforts to target PIM kinases for anticancer therapy have intensified in recent years. Clinical and preclinical studies indicate that pharmacologic inhibition of PIM has the potential to significantly improve the efficacy of standard and targeted therapies. This review focuses on the signaling pathways through which PIM kinases promote cancer progression and resistance to therapy, as well as highlights biological contexts and promising strategies to exploit PIM as a therapeutic target in cancer.