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Mutation Research. Reviews in Mutation... 2016The last 50 years, a variety of archaea and bacteria able to withstand extremely high doses of ionizing radiation, have been discovered. Several lines of evidence... (Review)
Review
The last 50 years, a variety of archaea and bacteria able to withstand extremely high doses of ionizing radiation, have been discovered. Several lines of evidence suggest a variety of mechanisms explaining the extreme radioresistance of microorganisms found usually in isolated environments on Earth. These findings are discussed thoroughly in this study. Although none of the strategies discussed here, appear to be universal against ionizing radiation, a general trend was found. There are two cellular mechanisms by which radioresistance is achieved: (a) protection of the proteome and DNA from damage induced by ionizing radiation and (b) recruitment of advanced and highly sophisticated DNA repair mechanisms, in order to reconstruct a fully functional genome. In this review, we critically discuss various protecting (antioxidant enzymes, presence or absence of certain elements, high metal ion or salt concentration etc.) and repair (Homologous Recombination, Single-Strand Annealing, Extended Synthesis-Dependent Strand Annealing) mechanisms that have been proposed to account for the extraordinary abilities of radioresistant organisms and the homologous radioresistance signature genes in these organisms. In addition, and based on structural comparative analysis of major radioresistant organisms, we suggest future directions and how humans could innately improve their resistance to radiation-induced toxicity, based on this knowledge.
Topics: Antioxidants; Archaea; Bacteria; DNA Damage; DNA Repair; Humans; Oxidation-Reduction; Radiation Tolerance; Radiation, Ionizing
PubMed: 27036069
DOI: 10.1016/j.mrrev.2015.10.001 -
Journal of Cancer Research and Clinical... Sep 2018Radiotherapy (RT) is one of the most important therapeutic strategies against cancer. However, resistance of cancer cells to radiation remains a major challenge for RT.... (Review)
Review
BACKGROUND
Radiotherapy (RT) is one of the most important therapeutic strategies against cancer. However, resistance of cancer cells to radiation remains a major challenge for RT. Thus, novel strategies to overcome cancer cell radioresistance are urgent. Macroautophagy (hereafter referred to as autophagy) is a biological process by which damaged cell components can be removed and accordingly represent a cytoprotective mechanism. Because radiation-induced autophagy is associated with either cell death or radioresistance of cancer cells, a deeper understanding of the autophagy mechanism triggered by radiation will expedite a development of strategies improving the efficacy of RT. MicroRNAs (miRNAs) are involved in many biological processes. Mounting evidence indicates that many miRNAs are involved in regulation of the autophagic process induced by radiation insult, but the underlying mechanisms remain obscure. Therefore, a deep understanding of the mechanisms of miRNAs in regulating autophagy and radioresistance will provide a new perspective for RT against cancer.
METHODS
We summarized the recent pertinent literature from various electronic databases, including PubMed. We reviewed the radiation-induced autophagy response and its association of the role, function and regulation of miRNAs, and discussed the feasibility of targeting autophagy-related miRNAs to improve the efficacy of RT.
CONCLUSION
The beneficial or harmful effect of autophagy may depend on the types of cancer and stress. The cytoprotective role of autophagy plays a dominant role in cancer RT. For most tumor cells, reducing radiation-induced autophagy can improve the efficacy of RT. MiRNAs have been confirmed to take part in the autophagy regulatory network of cancer RT, the autophagy-regulating miRNAs therefore could be developed as potential targets for improving RT.
Topics: Animals; Autophagy; Humans; MicroRNAs; Neoplasms; Radiation Tolerance; Radiotherapy
PubMed: 29971533
DOI: 10.1007/s00432-018-2675-8 -
European Journal of Nuclear Medicine... Feb 2019
Topics: Diagnostic Imaging; Female; Humans; Male; Radiation Dosage; Radiation Tolerance; Social Control, Formal
PubMed: 30560486
DOI: 10.1007/s00259-018-4233-7 -
Anti-cancer Agents in Medicinal... 2015Radiotherapy effectively destroys cancer cells in many sites of the body, but several limitations remain. This study investigated alternative splicing, which is a common... (Review)
Review
Radiotherapy effectively destroys cancer cells in many sites of the body, but several limitations remain. This study investigated alternative splicing, which is a common mechanism of increased diversity in mRNAs and proteins. The relationships of alternative splicing to DNA damage and radiation such as UV and ionizing radiation were analyzed. The DNA damage responses of many genes involved in alternative splicing were compared between non-radiation and radiation treatments. Drugs that affect radioresistence or radiosensitization by modulating the effects of alternative splicing and radiation were also reviewed.
Topics: Alternative Splicing; DNA Damage; Humans; Neoplasms; Pharmaceutical Preparations; RNA, Messenger; Radiation Tolerance
PubMed: 25902333
DOI: 10.2174/1871520615666150422145005 -
Cancer Metastasis Reviews Sep 2018During radiotherapy, an inflammatory response might be induced by activating various enzymes involved in membrane lipid metabolism. The eicosanoid pathway associated... (Review)
Review
During radiotherapy, an inflammatory response might be induced by activating various enzymes involved in membrane lipid metabolism. The eicosanoid pathway associated with cytosolic phospholipase A2 (cPLA), cyclooxygenases (COXs), and lipoxygenases (LOXs) can be induced by radiation, and many lipid metabolites might contribute to cancer-associated inflammation, cell proliferation, and cell survival in cancer. The lipid metabolites are also involved in the establishment of the tumor-associated microenvironment through promotion of angiogenesis and formation of vascular network. These biological activities of lipid metabolites are responsible for malignant progression with the acquisition of radioresistance, leading to unsatisfactory outcome of cancer radiotherapy. Many efforts have been made to identify the mechanisms associated with bioactive lipid metabolites and radiation signaling that lead to radioresistance and to develop potent radiosensitizers to improve therapeutic efficacy. Beneficial outcomes would be achieved by targeting the enzymes, such as cPLA, COXs, and LOXs, responsible for arachidonic acid metabolism and cancer-associated inflammation during cancer radiotherapy. The current study demonstrated a brief review for the radioresistant effects of bioactive lipid metabolites and their enzymes in cancer and the radiosensitizing effects of inhibitors for the enzymes on cancer therapy.
Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acids; Biomarkers; Clinical Trials as Topic; Combined Modality Therapy; Cyclooxygenase 2; Disease Susceptibility; Enzyme Activation; Gene Expression Regulation, Enzymologic; Humans; Lipid Metabolism; Neoplasms; Phospholipases A2, Cytosolic; Prognosis; Radiation Tolerance; Treatment Outcome
PubMed: 29971572
DOI: 10.1007/s10555-018-9742-0 -
International Journal of Oncology Nov 2014Radiation therapy is a staple cancer treatment approach that has significantly improved local disease control and the overall survival of cancer patients. However, its... (Review)
Review
Radiation therapy is a staple cancer treatment approach that has significantly improved local disease control and the overall survival of cancer patients. However, its efficacy is still limited by the development of radiation resistance and the presence of residual disease after therapy that leads to cancer recurrence. Radiation impedes cancer cell growth by inducing cytotoxicity, mainly caused by DNA damage. However, radiation can also simultaneously induce multiple pro-survival signaling pathways, such as those mediated by AKT, ERK and ATM/ATR, which can lead to suppression of apoptosis, induction of cell cycle arrest and/or initiation of DNA repair. These signaling pathways act conjointly to reduce the magnitude of radiation-induced cytotoxicity and promote the development of radioresistance in cancer cells. Thus, targeting these pro-survival pathways has great potential for the radiosensitization of cancer cells. In the present review, we summarize the current literature on how these radiation‑activated signaling pathways promote cancer cell survival.
Topics: Apoptosis; Cell Survival; Cell Transformation, Neoplastic; DNA Damage; Humans; Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents
PubMed: 25174607
DOI: 10.3892/ijo.2014.2614 -
Free Radical Biology & Medicine Nov 2015Nrf2 is a transcription factor that promotes antioxidant and drug-metabolizing gene expression. It also regulates the transcription of genes involved in carbohydrate and... (Review)
Review
Nrf2 is a transcription factor that promotes antioxidant and drug-metabolizing gene expression. It also regulates the transcription of genes involved in carbohydrate and lipid metabolism, NADPH regeneration, and heme and iron metabolism, as well as proteasome metabolism. Emerging research has identified Nrf2 as a critical factor for promoting survival of mammalian cells subjected to ionizing radiation. At a mechanistic level, Nrf2 promotes the repair of DNA damage and drives detoxification of superoxide that is generated hours to days after irradiation. This review summarizes research in these areas and discusses targeting of Nrf2 in radiation-resistant cancer and Nrf2׳s role in mitigating acute radiation syndrome.
Topics: Animals; Cell Survival; DNA Repair; Humans; NF-E2-Related Factor 2; Radiation Tolerance; Radiation, Ionizing
PubMed: 25975985
DOI: 10.1016/j.freeradbiomed.2015.04.035 -
PeerJ 2023Aerobic glycolysis is a metabolic mode of tumor cells different from normal cells that plays an important role in tumor proliferation and distant metastasis.... (Review)
Review
Aerobic glycolysis is a metabolic mode of tumor cells different from normal cells that plays an important role in tumor proliferation and distant metastasis. Radiotherapy has now become a routine and effective treatment for many malignancies, however, resistance to radiotherapy remains a major challenge in the treatment of malignant tumors. Recent studies have found that the abnormal activity of the aerobic glycolysis process in tumor cells is most likely involved in regulating chemoresistance and radiation therapy resistance in malignant tumors. However, research on the functions and mechanisms of aerobic glycolysis in the molecular mechanisms of resistance to radiotherapy in malignant tumors is still in its early stages. This review collects recent studies on the effects of aerobic glycolysis and radiation therapy resistance in malignant tumors, to further understand the progress in this area. This research may more effectively guide the clinical development of more powerful treatment plans for radiation therapy resistant subtypes of cancer patients, and take an important step to improve the disease control rate of radiation therapy resistant subtypes of cancer patients.
Topics: Humans; Neoplasms; Radiation Tolerance; Glycolysis
PubMed: 36811010
DOI: 10.7717/peerj.14930 -
Seminars in Radiation Oncology Oct 2017A complete understanding of the mechanisms of the response to radiation would help in a better evaluation of the radiation-induced risks. To this aim, individual... (Review)
Review
A complete understanding of the mechanisms of the response to radiation would help in a better evaluation of the radiation-induced risks. To this aim, individual radiosensitivity, that is, the proneness to radiation-induced tissue reactions attributable to cell death, has been documented since the beginning of the 20th century. For several decades, developing informative predictive assays has been one of the most important challenges of radiobiologists. This article is a critical review devoted to the major functional assays to predict radiosensitivity and their strengths and weaknesses, notably those based on the quantification of clonogenic cell survival, micronuclei, p21 expression, apoptosis, chromosome and DNA repair, and signaling. Genomic approaches of radiosensitivity are reviewed in another article of this issue.
Topics: Apoptosis; Cell Death; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; DNA Repair; Humans; Micronucleus Tests; Radiation Tolerance
PubMed: 28865513
DOI: 10.1016/j.semradonc.2017.04.003 -
Journal of Cancer Research and Clinical... May 2022Radiotherapy (RT) is considered as a standard in the treatment of most solid cancers, including glioblastoma, lung, breast, rectal, prostate, colorectal, cervical,... (Review)
Review
Radiotherapy (RT) is considered as a standard in the treatment of most solid cancers, including glioblastoma, lung, breast, rectal, prostate, colorectal, cervical, esophageal, and head and neck cancers. The main challenge in RT is tumor cell radioresistance associated with a high risk of locoregional relapse and distant metastasis. Despite significant progress in understanding mechanisms of radioresistance, its prediction and overcoming remain unresolved. This review presents the state-of-the-art for the potential universal biomarkers correlated to the radioresistance and poor outcome in different cancers. We describe radioresistance biomarkers functionally attributed to DNA repair, signal transduction, hypoxia, and angiogenesis. We also focus on high throughput genetic and proteomic studies, which revealed a set of molecular biomarkers related to radioresistance. In conclusion, we discuss biomarkers which are overlapped in most several cancers.
Topics: Biomarkers; Biomarkers, Tumor; Cell Line, Tumor; Head and Neck Neoplasms; Humans; Male; Neoplasm Recurrence, Local; Proteomics; Radiation Tolerance
PubMed: 35113235
DOI: 10.1007/s00432-022-03923-4