Byeong Mo Kim*, Wonsuck Yoon, Jung-Hyun Shim, Haiyoung Jung, Ji Hong Lim, Hyun-Jung Choi, MiRan Seo, Tae Ho Lee and Sang-Hyun Min* Pages 4259 - 4280 ( 22 )
Phosphorylation, the addition of a phosphate group to a molecule, is an effective way of regulating the biological properties of that molecule. Protein phosphorylation is a post-translational modification of proteins and affects cellular signaling transduction. Protein kinases induce phosphorylation by catalyzing the transfer of phosphate groups to serine, threonine, and tyrosine residues on protein substrates. Consistent with their roles in cancer, protein kinases have emerged as one of the most clinically useful target molecules in pharmacological cancer therapy. Intrinsic or acquired resistance of cancers against anti-cancer therapeutics, such as ionizing radiation, is a major obstacle for the effective treatment of many cancers. In this review, we describe key aspects of various kinases acting on proteins. We also discuss the roles of protein kinases in the pathophysiology and treatment of cancer. Because protein kinases correlate with radiation resistance in various types of cancer, we focus on several kinases responsible for radiation resistance and/or sensitivity and their therapeutic implications. Finally, we suggest some ongoing radiation-sensitization strategies using genetic loss and/or kinase inhibitors that can counteract radiation resistance-related protein kinases.
Kinase, protein, cancer, resistance, ionizing radiation, therapeutic target, radiation-sensitization strategies.
Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Allergy Immunology Center, College of Medicine, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Mokpo 534-729, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Department of Biomedical Chemistry, Konkuk University, 268 Chungwon-daero, Chungju, Chungbuk 27478, Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, New Drug Development Center, DGMIF, 80 Chumbok-ro, Dong-gu, Daegu 41061