Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies

The Proviral Integration site of Moloney murine leukemia virus (PIM) family of intracellular serine/threonine kinases (PIM1, PIM2, and PIM3) is implicated in the pathogenesis of many hematologic malignancies and solid tumors.1,2 PIM kinases are important downstream effectors of several oncogenic signaling pathways, such as those mediated by Janus kinase/signal transducers and activators of transcription (JAK/STAT), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), or nuclear factor-kB.1,3,4 In turn, PIM kinases regulate several key cellular functions including, but not limited to, apoptosis, cell cycle, cell proliferation, and cell migration by phosphorylating key substrates; for example, BCL-2 –associated death promoter protein (BAD), cyclin-dependent kinase inhibitor 1 (p21, p27), c-MYC, and eukaryotic initiation factor 4B.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research