PIM Kinases in Multiple Myeloma
Multiple myeloma (MM) remains an incurable disease and novel therapeutic agents/approaches are urgently needed. The PIM (Proviral insertion in murine malignancies) serine/threonine kinases have 3 isoforms: PIM1, PIM2, and PIM3. PIM kinases are engaged by having an expansive scope of biological activities including cell growth, apoptosis, drug resistance, and immune response. A variety of molecules and pathways which are important to myeloma tumorigenesis continues to be acknowledged as the downstream targets of PIM kinases. The inhibition of PIM kinases is becoming a growing scientific interest to treat multiple myeloma and many PIM kinase inhibitors, for example SGI-1776, AZD1208, and PIM447 (formerly LGH447), happen to be developed and therefore are under different phases of numerous studies. Current studies have concentrated on the introduction of a brand new generation of potent PIM kinase inhibitors with appropriate medicinal profiles cost effective for human malignancy treatment. Combination therapy of PIM kinase inhibitors with chemotherapeutic seems to produce an additive cytotoxic impact in cancer cells. Notwithstanding, the mechanisms through which PIM kinases modulate the immune microenvironment and synergize using the immunomodulatory agents for example lenalidomide haven’t been deliberately portrayed. This review supplies a comprehensive summary of the PIM kinase pathways and also the current research status of the introduction of PIM kinase inhibitors to treat MM. Furthermore, the combinatorial results of the PIM kinase inhibitors along with other targeted agents and also the promising ways of exploit PIM like a therapeutic target in malignancy are highlighted.