OncoTargets and Therapy (Apr 2023)
MNK Proteins as Therapeutic Targets in Leukemia
Abstract
Candice Mazewski,1,2 Leonidas C Platanias1– 3 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA; 2Division of Hematology–Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 3Department of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USACorrespondence: Candice Mazewski; Leonidas C Platanias, Email [email protected]; [email protected]: In leukemia, resistance to therapy is a major concern for survival. MAPK-interacting kinases (MNKs) have been identified as important activators of oncogenic-related signaling and may be mediators of resistance. Recent studies in leukemia models, especially acute myeloid leukemia (AML), have focused on targeting MNKs together with other inhibitors or treating chemotherapy-resistant cells with MNK inhibitors. The preclinical demonstrations of the efficacy of MNK inhibitors in these combination formats would suggest a promising potential for use in clinical trials. Optimizing MNK inhibitors and testing in leukemia models is actively being pursued and may have important implications for the future. These studies are furthering the understanding of the mechanisms of MNKs in cancer which could translate to clinical studies.Keywords: MNK, resistance, MAPK, eIF4E, AML