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.
Highlights
Radiation therapy is a useful cancer treatment strategy and is a highly cost-effective single-modality treatment
DNA damage monitoring and signaling systems are responsible for cell cycle arrest and checkpoint, and failure of these controls leads to cell death
MG-63 osteosarcoma spheroids die by apoptosis after exposure to 5 Gy Ionizing radiation (IR), while they die by necrosis after exposure to 30 Gy IR [38], suggesting that a much higher dose of IR triggers necrotic cell death
Summary
Radiation therapy is a useful cancer treatment strategy and is a highly cost-effective single-modality treatment. The resulting ions can kill or cause serious damage to cancer cells. External beam radiation therapies, such as X-rays and γ-rays, involve the targeting of radiation at the cancer in a specific part of the body. Internal radiation therapies based on the use of electrons, protons, neutrons, carbon ions, α particles, or β particles are treatments in which a source of radiation, either solid or liquid, is placed inside the body.Int. J. The biological effectiveness of IR in killing cancer cells depends on the type of radiation, total cancer, glioblastdoomse,afr,acstoiofntattioisnsruatee, acnadrcthientoamrgeate,daonrgdansad[1]v. IR therapy,2.lIiRk-eInoduthceedrCetyllpDeeasthoOfuatcnotmicesancer treatments, may induce multiple forms of cancer cell death through a vaIrRiethteyrapoyf, lmikeooltehceur tlyapresmofeacnhticaannciesrmtresa.tmSeentvs,emraayl imndoucde emsulotifplecefolrlmksiolflicnangc,erscuelcl h as apoptosis, necrosis, autophdaeagthy,thmroiutgohtaicvacraiettaysotfrmooplehcuel,aramnedchsaennismess.cSeenvecreal, moocdceus rofacfetllekrilelinxgp, souscuh raes atpoopItRosi(sF, igure 1). There is evidence that necroptosis is involved in IR-induced cancer cell death, the role of this type of death is a very inchoate area of research (novel mechanism of IR-induced cell death?)
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