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The British Journal of Radiology Jan 2017Tumours contain multiple different cell populations, including cells derived from the bone marrow as well as cancer-associated fibroblasts and various stromal... (Review)
Review
Tumours contain multiple different cell populations, including cells derived from the bone marrow as well as cancer-associated fibroblasts and various stromal populations including the vasculature. The microenvironment of the tumour cells plays a significant role in the response of the tumour to radiation treatment. Low levels of oxygen (hypoxia) caused by the poorly organized vasculature in tumours have long been known to affect radiation response; however, other aspects of the microenvironment may also play important roles. This article reviews some of the old literature concerning tumour response to irradiation and relates this to current concepts about the role of the tumour microenvironment in tumour response to radiation treatment. Included in the discussion are the role of cancer stem cells, radiation damage to the vasculature and the potential for radiation to enhance immune activity against tumour cells. Radiation treatment can cause a significant influx of bone marrow-derived cell populations into both normal tissues and tumours. Potential roles of such cells may include enhancing vascular recovery as well as modulating immune reactivity.
Topics: Animals; Cell Cycle; Cell Death; Cell Hypoxia; Cell Survival; Humans; Neoplasms; Neoplastic Stem Cells; Radiation Dosage; Radiation Tolerance; Tumor Cells, Cultured; Tumor Microenvironment
PubMed: 27416998
DOI: 10.1259/bjr.20160474 -
Molecular Microbiology Jan 2024Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive.... (Review)
Review
Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive. Desiccation is one of the most common and frequently encountered stresses in nature. On the contrary, ionizing radiations are limited to high local concentrations of naturally occurring radioactive materials and related anthropogenic activities. Yet, resistance to high doses of ionizing radiation is evident across the tree of life. The evolution of desiccation resistance has been linked to the evolution of ionizing radiation resistance, although, evidence to support the idea that the evolution of desiccation tolerance is a necessary precursor to ionizing radiation resistance is lacking. Moreover, the presence of radioresistance in hyperthermophiles suggests multiple paths lead to radiation resistance. In this minireview, we focus on the molecular aspects of damage dynamics and damage response pathways comprising protective and restorative functions with a definitive survival advantage, to explore the serendipitous genesis of ionizing radiation resistance.
Topics: Radiation, Ionizing; Deinococcus; Radiation Tolerance; DNA Repair
PubMed: 38082498
DOI: 10.1111/mmi.15208 -
International Review of Cell and... 2024Radiation therapy is a cornerstone of modern cancer treatment. Treatment is based on depositing focal radiation to the tumor to inhibit cell growth, proliferation and... (Review)
Review
Radiation therapy is a cornerstone of modern cancer treatment. Treatment is based on depositing focal radiation to the tumor to inhibit cell growth, proliferation and metastasis, and to promote the death of cancer cells. In addition, radiation also affects non-tumor cells in the tumor microenvironmental (TME). Radiation resistance of the tumor cells is the most common cause of treatment failure, allowing survival of cancer cell and subsequent tumor growing. Molecular radioresistance comprises genetic and epigenetic characteristics inherent in cancer cells, or characteristics acquired after exposure to radiation. Furthermore, cancer stem cells (CSCs) and non-tumor cells into the TME as stromal and immune cells have a role in promoting and maintaining radioresistant tumor phenotypes. Different regulatory molecules and pathways distinctive of radiation resistance include DNA repair, survival signaling and cell death pathways. Epigenetic mechanisms are one of the most relevant events that occur after radiotherapy to regulate the expression and function of key genes and proteins in the differential radiation-response. This article reviews recent data on the main molecular mechanisms and signaling pathways related to the biological response to radiotherapy in cancer; highlighting the epigenetic control exerted by DNA methylation, histone marks, chromatin remodeling and m6A RNA methylation on gene expression and activation of signaling pathways related to radiation therapy response.
Topics: Humans; Radiation Tolerance; Neoplasms; Epigenesis, Genetic; DNA Methylation; DNA Repair
PubMed: 38359968
DOI: 10.1016/bs.ircmb.2023.07.008 -
Seminars in Oncology Jun 2019Primary organ-confined prostate cancer is curable with external-beam radiotherapy. However, prostate cancer expresses a unique radiobiological phenotype, and its... (Review)
Review
Primary organ-confined prostate cancer is curable with external-beam radiotherapy. However, prostate cancer expresses a unique radiobiological phenotype, and its ablation requires doses at the high-end range of clinical radiotherapy. At this dose level, normal tissue radiosensitivity restricts the application of curative treatment, and mandates the use of the most advanced high-precision treatment delivery techniques to spare critical organs at risk. The efficacy and tolerance of dose-escalated conventional fractionated radiotherapy and of the biological equivalent doses of moderate and extreme hypofractionation are reviewed. Current studies indicate that novel risk-adapted techniques to spare normal organs at risk are still required to deploy high-biological equivalent dose extreme hypofractionation, while affording preservation of quality of life and cost-effectiveness.
Topics: Dose-Response Relationship, Radiation; Humans; Male; Prostate; Prostatic Neoplasms; Radiation Dosage; Radiation Tolerance
PubMed: 31492437
DOI: 10.1053/j.seminoncol.2019.08.001 -
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 -
The Science of the Total Environment Mar 2024Adaptation to environmental stressors is an essential property of plants that allows them, despite an immobile lifestyle, to survive in a changeable environment. The... (Review)
Review
Adaptation to environmental stressors is an essential property of plants that allows them, despite an immobile lifestyle, to survive in a changeable environment. The chain of successive events culminating in the final radiobiological reaction begins with the absorption of energy of ionizing radiation in the cell. Starting from stochastic acts of molecular injury formation, radiation damage gradually acquires deterministic features, which are expressed in a limited number of phenomena that complete plant radiation damage. As plants undergo specialization, the differences between plants and animals become more pronounced, leading to distinct responses to radiation. Chronic radiation exposure may activate biological mechanisms resulting in increased radioresistance of the population. The higher the level of radiation exposure and the sensitivity of plants to radiation, the more intensive the selection. Depending on the circumstances, enhanced radioresistance of a population can be achieved in different ways or has not evolved at all. High dose rates of chronic irradiation leаd to selection for the efficiency of repair systems, while low dose rates activate epigenetic mechanisms that lead to the maintenance of oxidative balance, additional synthesis of chaperones, and control of TEs transposition. Due to huge differences in the radiosensitivity of organisms that make up the ecosystem, irradiation can result in disruption of connections between components of ecosystems which may lead to consequences that can differ drastically from those expected at the organismal and population levels. Therefore, the use of ecological knowledge is essential for understanding the responses of populations and ecosystems to radiation exposure.
Topics: Animals; Ecosystem; Radiation, Ionizing; Radiation Tolerance; Epigenesis, Genetic
PubMed: 38246389
DOI: 10.1016/j.scitotenv.2024.170201 -
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 -
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 -
The Lancet. Oncology May 2017Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all... (Review)
Review
Radiotherapy has long been the mainstay of treatment for patients with head and neck cancer and has traditionally involved a stage-dependent strategy whereby all patients with the same TNM stage receive the same therapy. We believe there is a substantial opportunity to improve radiotherapy delivery beyond just technological and anatomical precision. In this Series paper, we explore several new ideas that could improve understanding of the phenotypic and genotypic differences that exist between patients and their tumours. We discuss how exploiting these differences and taking advantage of precision medicine tools-such as genomics, radiomics, and mathematical modelling-could open new doors to personalised radiotherapy adaptation and treatment. We propose a new treatment shift that moves away from an era of empirical dosing and fractionation to an era focused on the development of evidence to guide personalisation and biological adaptation of radiotherapy. We believe these approaches offer the potential to improve outcomes and reduce toxicity.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Genotype; Head and Neck Neoplasms; Humans; Immunotherapy; Models, Theoretical; Phenotype; Precision Medicine; Radiation Tolerance; Radiotherapy; Radiotherapy Dosage
PubMed: 28456586
DOI: 10.1016/S1470-2045(17)30252-8 -
Radiation Oncology (London, England) Mar 2017Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly,... (Review)
Review
Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed.
Topics: Animals; Autophagy; Humans; Neoplasms; Radiation Tolerance
PubMed: 28320471
DOI: 10.1186/s13014-017-0795-y