title: Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy.
abstract: Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.
authors.affiliation: Severance Integrative Research Institute for Cerebral & Cardiovascular Diseases (SIRIC), Yonsei University College of Medicine, Seoul 03722, Korea. bkimtwo@gmail.com.
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.affiliation: Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University, Gimhae 50834, Korea. dangmoo777@naver.com.|Biohealth Products Research Center (BPRC), Inje University, Gimhae 50834, Korea. dangmoo777@naver.com.|Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae 50834, Korea. dangmoo777@naver.com.
authors.forename: Yunkyung
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University, Gimhae 50834, Korea. stormyboy@nate.com.|Biohealth Products Research Center (BPRC), Inje University, Gimhae 50834, Korea. stormyboy@nate.com.|Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae 50834, Korea. stormyboy@nate.com.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. pengdaliu@gmail.com.
authors.forename: Pengda
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea. jhlim@kku.ac.kr.
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Biomedical Laboratory Science, Dongseo University, Busan 617-716, Korea. yhlee@gdsu.dongseo.ac.kr.
authors.forename: Yong Heon
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. tlee3@bidmc.harvard.edu.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Lee
authors.affiliation: National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 28116, Korea. changkt@kribb.re.kr.
authors.forename: Kyu Tae
authors.initials: KT
authors.lastname: Chang
authors.affiliation: Department of Physical Therapy, College of Biomedical Science & Engineering, Inje University, Gimhae 50834, Korea. yonghong@inje.ac.kr.|Biohealth Products Research Center (BPRC), Inje University, Gimhae 50834, Korea. yonghong@inje.ac.kr.|Ubiquitous Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gimhae 50834, Korea. yonghong@inje.ac.kr.|Department of Rehabilitation Science, Graduate School of Inje University, Gimhae 50834, Korea. yonghong@inje.ac.kr.
authors.forename: Yonggeun
authors.initials: Y
authors.lastname: Hong
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001343:Autophagy / Q000235:genetics / Q000528:radiation effects; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy / Q000379:methods*; D020732:Cytogenetic Analysis; D004249:DNA Damage / Q000528:radiation effects; D005720:Gamma Rays / Q000627:therapeutic use*; D042822:Genomic Instability; D006801:Humans; D008938:Mitosis / Q000528:radiation effects; D009336:Necrosis / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014964:X-Ray Therapy
chemical_list: D011838:Radiation-Sensitizing Agents
keywords: DNA damage; cancer therapy; cell death; ionizing radiation (IR); prognostic markers; resistance; therapeutic targets