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Nature Reviews. Clinical Oncology Feb 2023Owing to advances in radiotherapy, the physical properties of radiation can be optimized to enable individualized treatment; however, optimization is rarely based on... (Review)
Review
Owing to advances in radiotherapy, the physical properties of radiation can be optimized to enable individualized treatment; however, optimization is rarely based on biological properties and, therefore, treatments are generally planned with the assumption that all tumours respond similarly to radiation. Radiation affects multiple cellular pathways, including DNA damage, hypoxia, proliferation, stem cell phenotype and immune response. In this Review, we summarize the effect of these pathways on tumour responses to radiotherapy and the current state of research on genomic classifiers designed to exploit these variations to inform treatment decisions. We also discuss whether advances in genomics have generated evidence that could be practice changing and whether advances in genomics are now ready to be used to guide the delivery of radiotherapy alone or in combination.
Topics: Humans; Radiation Tolerance; Neoplasms; Radiation Oncology; Genomics; Radiotherapy
PubMed: 36477705
DOI: 10.1038/s41571-022-00709-y -
Journal of Thoracic Oncology : Official... May 2021
Topics: Genomics; Humans; Lung Neoplasms; Prescriptions; Radiation Tolerance
PubMed: 33896574
DOI: 10.1016/j.jtho.2021.02.027 -
The Journal of Pathology Apr 2020Normal tissue responses to ionizing radiation have been a major subject for study since the discovery of X-rays at the end of the 19th century. Shortly thereafter,... (Review)
Review
Normal tissue responses to ionizing radiation have been a major subject for study since the discovery of X-rays at the end of the 19th century. Shortly thereafter, time-dose relationships were established for some normal tissue endpoints that led to investigations into how the size of dose per fraction and the quality of radiation affected outcome. The assessment of the radiosensitivity of bone marrow stem cells using colony-forming assays by Till and McCulloch prompted the establishment of in situ clonogenic assays for other tissues that added to the radiobiology toolbox. These clonogenic and functional endpoints enabled mathematical modeling to be performed that elucidated how tissue structure, and in particular turnover time, impacted clinically relevant fractionated radiation schedules. More recently, lineage tracing technology, advanced imaging and single cell sequencing have shed further light on the behavior of cells within stem, and other, cellular compartments, both in homeostasis and after radiation damage. The discovery of heterogeneity within the stem cell compartment and plasticity in response to injury have added new dimensions to the consideration of radiation-induced tissue damage. Clinically, radiobiology of the 20th century garnered wisdom relevant to photon treatments delivered to a fairly wide field at around 2 Gy per fraction, 5 days per week, for 5-7 weeks. Recently, the scope of radiobiology has been extended by advances in technology, imaging and computing, as well as by the use of charged particles. These allow radiation to be delivered more precisely to tumors while minimizing the amount of normal tissue receiving high doses. One result has been an increase in the use of schedules with higher doses per fraction given in a shorter time frame (hypofractionation). We are unable to cover these new technologies in detail in this review, just as we must omit low-dose stochastic effects, and many aspects of dose, dose rate and radiation quality. We argue that structural diversity and plasticity within tissue compartments provides a general context for discussion of most radiation responses, while acknowledging many omissions. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Topics: Acute Radiation Syndrome; DNA Damage; Dose-Response Relationship, Radiation; Humans; Neoplasms; Radiation Tolerance; Time Factors
PubMed: 31990369
DOI: 10.1002/path.5389 -
Laryngo- Rhino- Otologie Sep 2023
Topics: Humans; Laryngeal Neoplasms; Larynx; Radiation Tolerance
PubMed: 37657431
DOI: 10.1055/a-2093-2445 -
Tumour Biology : the Journal of the... Jun 2015Autophagy differs from apoptosis and is independent of phagocytes by the appearance of autophagosomes, autolysosomes, and complete nuclei in the cell. This process... (Review)
Review
Autophagy differs from apoptosis and is independent of phagocytes by the appearance of autophagosomes, autolysosomes, and complete nuclei in the cell. This process significantly contributes to the antineoplastic effects of radiation. Radiation is an important strategy in cancer treatment; however, many types of cancer show radioresistance. The effects of radiotherapy are affected by factors, including the degree of tumor tissue hypoxia, the ability to repair DNA damage, and the presence of cancer stem cells. We review the relationships among autophagy, the three factors in cancer radiation, and the possible underlying molecular mechanisms. The therapeutic implications of these relationships and mechanisms in clinical settings are also discussed.
Topics: Apoptosis; Autophagy; Cell Hypoxia; DNA Damage; Humans; Neoplasms; Neoplastic Stem Cells; Radiation Tolerance
PubMed: 25946972
DOI: 10.1007/s13277-015-3496-x -
Radiation Research Jan 2022Recent epidemiological and experimental animal data, as well as reanalyses of data previously accumulated, indicate that the lens of the eye is more radiosensitive than...
Recent epidemiological and experimental animal data, as well as reanalyses of data previously accumulated, indicate that the lens of the eye is more radiosensitive than was previously thought. This has resulted in a reduction of the occupational lens dose limit within the European Union countries, Japan and elsewhere. This Commentary introduces the work done by the LDLensRad Consortium contained within this Focus Issue, towards advancement of understanding of the mechanisms of low dose radiation cataract.
Topics: Animals; Cataract; Dose-Response Relationship, Radiation; Europe; Humans; Japan; Lens, Crystalline; Mice, Inbred C57BL; Occupational Exposure; Radiation Dosage; Radiation Tolerance; Mice
PubMed: 34788470
DOI: 10.1667/RADE-21-00188.1 -
Cancer Radiotherapie : Journal de La... 2022The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to...
The place of personalized treatments is highly increasing in medical and radiation oncology. During the last decades, a huge number of assays have been developed to predict responses of normal tissues and tumours. These tests have not yet been included into daily clinical practice but the recent developments of radiation oncology are paving the way of personalized strategies including the risk of tumour recurrence and normal tissue reactions. Concerning tumor radiosensitivity prediction, no test are currently used, even if the radiosensitivity index and the genome-based model for adjusting radiotherapy dose assays seem the most promising with level II of evidence. Commercial developments are under progress. Concerning normal tissue radiosensitivity prediction, single nucleotide polymorphims of prostate cancer patients and radiation-induced CD8 T-lymphocyte apoptosis breast and prostate assays are of level I of evidence. They can be proposed before the beginning of radiotherapy in order to propose personalized treatments according to both risks of tumour and normal tissue radiosensitivity. Commercial developments are also under way.
Topics: DNA Repair; Fibroblasts; Gene Expression; Genetic Markers; Humans; Neoplasms; Organs at Risk; Polymorphism, Single Nucleotide; Precision Medicine; Prognosis; Radiation Tolerance; Treatment Outcome
PubMed: 34953704
DOI: 10.1016/j.canrad.2021.11.008 -
Lung Cancer (Amsterdam, Netherlands) Feb 2023Huge technological and biomedical advances have improved the survival and quality of life of lung cancer patients treated with radiotherapy. However, during treatment... (Review)
Review
Huge technological and biomedical advances have improved the survival and quality of life of lung cancer patients treated with radiotherapy. However, during treatment planning, a probability that the patient will experience adverse effects is assumed. Radiotoxicity is a complex entity that is largely dose-dependent but also has important intrinsic factors. One of the most studied is the genetic variants that may be associated with susceptibility to the development of adverse effects of radiotherapy. This review aims to present the current status of radiogenomics in lung cancer, integrating results obtained in association studies of SNPs (single nucleotide polymorphisms) related to radiotherapy toxicities. We conclude that despite numerous publications in this field, methodologies and endpoints vary greatly, making comparisons between studies difficult. Analyzing SNPs from the candidate gene approach, together with the study in cohorts limited by the sample size, has complicated the possibility of having validated results. All this delays the incorporation of genetic biomarkers in predictive models for clinical application. Thus, from all analysed SNPs, only 12 have great potential as esophagitis genetic risk factors and deserve further exploration. This review highlights the efforts that have been made to date in the radiogenomic study of radiotoxicity in lung cancer.
Topics: Humans; Lung Neoplasms; Polymorphism, Single Nucleotide; Quality of Life; Radiation Genomics; Radiation Injuries; Radiation Oncology; Radiation Tolerance
PubMed: 36621035
DOI: 10.1016/j.lungcan.2023.01.001 -
Anticancer Research May 2015Radiation therapy is essential for local tumor control for many types of cancer histologies. Technological advancements in recent years have allowed for precise... (Review)
Review
Radiation therapy is essential for local tumor control for many types of cancer histologies. Technological advancements in recent years have allowed for precise irradiation of target tissues while minimizing the dose to non-target tissues. To enhance radiation damage to cancer cells and further limit the radiation effects on normal tissue, researchers have explored compounds that specifically target cancer cells and make them more sensitive to ionizing radiation. Recent radiosensitization research has focused on promising compounds that alter hypoxia, inhibit topoisomerases, interfere with microtubules, and activate caspases, among other mechanisms. Many such compounds have shown impressive results in pre-clinical trials against a variety of cell types, but their safety, efficacy and practicability in clinical trials remains to be demonstrated. This review seeks to provide an overview of recent research in radiosensitization, detailing some of the more successful compounds, and illustrating avenues for future research.
Topics: Cell Hypoxia; Humans; Neoplasms; Radiation Tolerance; Radiation, Ionizing; Radiation-Sensitizing Agents; Topoisomerase Inhibitors
PubMed: 25964520
DOI: No ID Found -
Radiotherapy and Oncology : Journal of... Sep 2017The utilization of gold nanoparticles (AuNPs) as radiosensitizers has shown great promise in pre-clinical research. In the current review, the physical, chemical, and... (Review)
Review
The utilization of gold nanoparticles (AuNPs) as radiosensitizers has shown great promise in pre-clinical research. In the current review, the physical, chemical, and biological pathways via which AuNPs enhance the effects of radiation are presented and discussed. In particular, the impact of AuNPs on the 5 Rs in radiobiology, namely repair, reoxygenation, redistribution, repopulation, and intrinsic radiosensitivity, which determine the extent of radiation enhancement effects are elucidated. Key findings from previous studies are outlined. In addition, crucial parameters including the physicochemical properties of AuNPs, route of administration, dosing schedule of AuNPs and irradiation, as well as type of radiation therapy, are highlighted; the optimal selection and combination of these parameters enable the achievement of a greater therapeutic window for AuNP sensitized radiotherapy. Future directions are put forward as a means to provide guidelines for successful translation of AuNPs to clinical applications as radiosensitizers.
Topics: Animals; Gold; Humans; Metal Nanoparticles; Radiation Tolerance; Radiation-Sensitizing Agents
PubMed: 28784439
DOI: 10.1016/j.radonc.2017.07.007