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International Journal of Molecular... Mar 2020Radiotherapy is an essential component of cancer therapy and remains one of the most (cost-) effective treatment options available [...].
Radiotherapy is an essential component of cancer therapy and remains one of the most (cost-) effective treatment options available [...].
Topics: Humans; Neoplasms; Radiation Tolerance; Radiotherapy
PubMed: 32150868
DOI: 10.3390/ijms21051767 -
Molecular Cancer Mar 2020Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been... (Review)
Review
Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.
Topics: Animals; Biomarkers, Tumor; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; RNA, Circular; Radiation Tolerance
PubMed: 32171304
DOI: 10.1186/s12943-020-01180-y -
Cells Apr 2021bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or... (Review)
Review
bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or prolonged desiccation. An efficient, SOS-independent response mechanism to induce various DNA repair genes such as is essential for radiation resistance. This pathway, called radiation/desiccation response, is controlled by metallopeptidase IrrE and repressor DdrO that are highly conserved in . Among various species, has been studied most extensively. Its genome encodes classical DNA repair proteins for error-free repair but no error-prone translesion DNA polymerases, which may suggest that absence of mutagenic lesion bypass is crucial for error-free repair of massive DNA damage. However, many other radiation-resistant species do possess translesion polymerases, and radiation-induced mutagenesis has been demonstrated. At least dozens of species contain a mutagenesis cassette, and some even two cassettes, encoding error-prone translesion polymerase DnaE2 and two other proteins, ImuY and ImuB-C, that are probable accessory factors required for DnaE2 activity. Expression of this mutagenesis cassette is under control of the SOS regulators RecA and LexA. In this paper, we review both the RecA/LexA-controlled mutagenesis and the IrrE/DdrO-controlled radiation/desiccation response in .
Topics: DNA Repair; Deinococcus; Gene Expression Regulation, Bacterial; Mutagenesis; Radiation Tolerance; SOS Response, Genetics
PubMed: 33923690
DOI: 10.3390/cells10040924 -
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 -
International Journal of Molecular... Sep 2022Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance,... (Review)
Review
Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer.
Topics: Cell Line, Tumor; Humans; Hypoxia; Mitochondria; Neoplasms; Radiation Tolerance; Reactive Oxygen Species
PubMed: 36232638
DOI: 10.3390/ijms231911343 -
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 -
Journal of Experimental & Clinical... Jan 2020Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and...
Low oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy selecting a more malignant and invasive phenotype, and playing a negative role in patient prognosis. This commentary wishes to recognize the 2019 Nobel Prize in Medicine awarded to three physicians-scientists, Prof. William G. Kaelin Jr., Prof. Sir Peter J. Ratcliffe, and Prof. Gregg L. Semenza, for their discovery of the mechanisms mediating cell ability to sense and adapt to changes in oxygen availability. Their studies established the basis for our understanding of the role of hypoxia in a variety of diseases, including anemia, renal failure, cardiovascular disease, metabolic diseases, and cancer, paving the way for new promising therapeutic strategies through the development of drugs that can either activate or block the oxygen-sensing machinery.
Topics: Antineoplastic Agents; Awards and Prizes; Drug Development; Drug Resistance, Neoplasm; Humans; Neoplasms; Radiation Tolerance; Tumor Hypoxia
PubMed: 31924239
DOI: 10.1186/s13046-019-1517-0 -
International Journal of Molecular... Aug 2022The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique... (Review)
Review
The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique susceptibility of the exposed individual. A critical target of IR is DNA, and the DNA damage response is a safeguard mechanism for maintaining genomic integrity in response to the induced cellular stress. Unrepaired DNA lesions lead to various mutations, contributing to adverse health effects. Cellular sensitivity to IR is highly correlated with the ability of cells to repair DNA lesions, in particular coding sequences of genes that affect that process and of others that contribute to preserving genomic integrity. However, accurate profiling of the molecular events underlying individual sensitivity requires techniques with sensitive readouts. Here we summarize recent studies that have used whole-genome analysis and identified genes that impact individual radiosensitivity. Whereas microarray and RNA-seq provide a snapshot of the transcriptome, RNA interference (RNAi) and CRISPR-Cas9 techniques are powerful tools that enable modulation of gene expression and characterizing the function of specific genes involved in radiosensitivity or radioresistance. Notably, CRISPR-Cas9 has altered the landscape of genome-editing technology with its increased readiness, precision, and sensitivity. Identifying critical regulators of cellular radiosensitivity would help tailor regimens that enhance the efficacy of therapeutic treatments and fast-track prediction of clinical outcomes. It would also contribute to occupational protection based on average individual sensitivity, as well as the formulation of countermeasures to the harmful effects of radiation.
Topics: CRISPR-Cas Systems; DNA; Gene Editing; Genetic Testing; Humans; Radiation Tolerance
PubMed: 35955908
DOI: 10.3390/ijms23158774 -
International Journal of Radiation... Aug 2017With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is... (Review)
Review
With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy. Therefore, the combination of radiation therapy and bioreductive drugs presents an attractive opportunity for synergistic effects, because the HAP targets the radiation-resistant hypoxic cells. Hypoxia-activated prodrugs have typically been precursors of DNA-damaging agents, but a new generation of molecularly targeted HAPs is emerging. By targeting proteins associated with tumorigenesis and survival, these compounds may result in greater selectivity over healthy tissue. We review the clinical progress of HAPs as adjuncts to radiation therapy and conclude that the use of HAPs alongside radiation is vastly underexplored at the clinical level.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Combined Modality Therapy; Humans; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasms; Phenotype; Prodrugs; Radiation Tolerance; Tumor Hypoxia
PubMed: 28721903
DOI: 10.1016/j.ijrobp.2017.03.024 -
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