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BMJ (Clinical Research Ed.) Jun 1992
Review
Topics: Combined Modality Therapy; Humans; Neoplasms; Particle Accelerators; Radiation Tolerance
PubMed: 1628059
DOI: 10.1136/bmj.304.6841.1554 -
International Journal of Molecular... Sep 2022Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current... (Review)
Review
Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current bottleneck in the development of radiation oncology. Circular RNAs (circRNAs) are a special class of endogenous non-coding RNAs. Numerous studies have shown that circRNAs have shown great potential in regulating the biological functions of tumors, including proliferation, migration, invasion, and treatment resistance, and that differences in their expression levels are closely related to the clinical prognosis of tumor patients. This review systematically compares the mechanisms of circRNAs in the process of tumor development and radiosensitivity and provides insight into the clinical translation of circRNAs in radiotherapy.
Topics: Humans; Neoplasms; RNA; RNA, Circular; Radiation Tolerance
PubMed: 36142355
DOI: 10.3390/ijms231810444 -
Trends in Genetics : TIG Jan 2023Ionizing radiation (IR)-induced DNA damage and repair are complex and occur at hierarchical chromatin structures; radiobiology needs to be studied from a 3D-genomic...
Ionizing radiation (IR)-induced DNA damage and repair are complex and occur at hierarchical chromatin structures; radiobiology needs to be studied from a 3D-genomic perspective. Differences in IR damage and repair throughout the 3D genome may help to explain differences in radiosensitivity.
Topics: DNA Repair; DNA Damage; Radiation, Ionizing; Radiation Tolerance; Genomics
PubMed: 35934594
DOI: 10.1016/j.tig.2022.07.004 -
Cancer Biology & Therapy Nov 2009Radiosensitivity can be influenced both by factors intrinsic and extrinsic to the cancer cell. One of the factors in the tumor microenvironment (TME) extrinsic to the... (Review)
Review
Radiosensitivity can be influenced both by factors intrinsic and extrinsic to the cancer cell. One of the factors in the tumor microenvironment (TME) extrinsic to the cancer cell that can affect radiosensitivity is oxygenation. Severely hypoxic cells require a 2-3 fold higher dose of radiation to achieve the same level of cell killing as do well-oxygenated cells. Other elements in the microenvironment that may influence tumor radiosensitivity are the response of stromal cells to radiation and the expression of factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1). There are currently several classes of agents that may increase tumor radiosensitivity by modulating the TME. Pre-clinical evidence indicates that inhibition of VEGF may increase local control after radiation. Several mechanisms have been postulated to explain this including radiosensitization of tumor endothelial cells, prevention of the establishment of new vasculature post-radiation, and increased oxygenation secondary to vascular normalization. Agents targeting HIF-1 also increase local control after radiation in pre-clinical models. This may occur via indirect inhibition of VEGF, which is a downstream target of HIF-1, or by VEGF-independent means. When combined with radiation, the EGFR inhibitor cetuximab improves local control and survival in patients with head and neck cancer. Pre-clinical data indicate that EGFR inhibitors can increase the intrinsic radiosensitivity of cancer cells. They can also improve tumor blood flow and oxygenation, which may increase extrinsic radiosensitivity. One of the pathways downstream of EGFR that may contribute to this effect is the PI3K/Akt pathway. Agents that directly inhibit this pathway improve blood flow and increase tumor oxygenation in pre-clinical models. The challenge remains to obtain clinical data from patients showing that modulation of the TME is an important mechanism by which biological agents can radiosensitize tumors and then to utilize this information to optimize therapy.
Topics: Animals; Cell Hypoxia; Humans; Neoplasms; Oxygen; Radiation Tolerance; Radiation-Sensitizing Agents; Signal Transduction
PubMed: 19823031
DOI: 10.4161/cbt.8.21.9988 -
Physics in Medicine and Biology Dec 2022Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.We...
Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent of SRD and its impact on cell survival.Significant accumulation of SRD begins at doses below 1 Gy. As dose increases, so does the number of damaged cells and the amount of SRD in individual cells. SRD buildup in a cell increases the likelihood of complex irrepairable damage. For this reason, during a dose fraction delivery, each dose increment makes cells more radiosensitive. This gradual radosensitization is evidenced by the increasing slope of survival curves observed experimentally. It continues until the fraction is delivered, unless radiosensitivity reaches its maximum first. The maximum radiosensitivity is achieved when SRD accumulated in most cells is the maximum damage they can repair. After this maximum is reached, the slope of a survival curve, logarithm of survival versus dose, becomes constant, dose independent. The survival curve becomes a straight line, as experimental data at high doses show. These processes are random. They cause large cell-to-cell variability in the extent of damage and radiosensitivity of individual cells.SRD is in effect a radiosensitizer and its accumulation is a significant factor affecting cell survival, especially at high doses. We developed a novel formalism to study this phenomena and reported pertinent data for several particle types.
Topics: Cell Survival; Dose-Response Relationship, Radiation; Radiation Tolerance; Protons; Photons; Relative Biological Effectiveness
PubMed: 36533628
DOI: 10.1088/1361-6560/aca5e7 -
Seminars in Radiation Oncology Apr 2009The tolerance of normal brain tissues limits the radiation dose that can be delivered safely during cranial radiotherapy, and one of the potential complications that can... (Review)
Review
The tolerance of normal brain tissues limits the radiation dose that can be delivered safely during cranial radiotherapy, and one of the potential complications that can arise involves cognitive impairment. Extensive laboratory data have appeared recently showing that hippocampal neurogenesis is significantly impacted by irradiation and that such changes are associated with altered cognitive function and involve, in part, changes in the microenvironment (oxidative stress and inflammation). Although there is considerable uncertainty about exactly how these changes evolve, new in vitro and in vivo approaches have provided a means by which new mechanistic insights can be gained relevant to the topic. Together, the data from cell culture and animal-based studies provide complementary information relevant to a potentially serious complication of cranial radiotherapy and should enhance our understanding of the tolerance of normal brain after cranial irradiation.
Topics: Animals; Brain; Brain Neoplasms; Central Nervous System; Humans; Mice; Neurons; Radiation Injuries; Radiation Tolerance; Stem Cells
PubMed: 19249650
DOI: 10.1016/j.semradonc.2008.12.003 -
Journal of Experimental & Clinical... Apr 2018Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of... (Review)
Review
BACKGROUND
Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation.
MAIN BODY
Here, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways.
SHORT CONCLUSION
The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
Topics: Humans; Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents
PubMed: 29688867
DOI: 10.1186/s13046-018-0758-7 -
Future Oncology (London, England) Oct 2010Based on findings that cancer cell clonogens exhibit stem cell features, it has been suggested that cancer stem-like cells are relatively radioresistant owing to... (Review)
Review
Based on findings that cancer cell clonogens exhibit stem cell features, it has been suggested that cancer stem-like cells are relatively radioresistant owing to different intrinsic and extrinsic factors, including quiescence, activated radiation response mechanisms (e.g., enhanced DNA repair, upregulated cell cycle control mechanisms and increased free-radical scavengers) and a surrounding microenvironment that enhances cell survival mechanisms (e.g., hypoxia and interaction with stromal elements). However, these radiosensitivity features are probably dynamic in nature and come into play at different times during the course of chemo/radiotherapy. Therefore, different molecularly targeted radiosensitization strategies may be needed at different stages of therapy. This article describes potential sensitization approaches based on the dynamics and changing properties of cancer stem-like cells during therapy.
Topics: Animals; Humans; Neoplastic Stem Cells; Radiation Tolerance
PubMed: 21062156
DOI: 10.2217/fon.10.121 -
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 -
Cancer Letters Aug 2021MRE11, the core of the MRE11/RAD50/NBS1 complex, is one of key DNA damage response proteins. Increasing evidence suggests that its expression in cancer cells is critical... (Review)
Review
MRE11, the core of the MRE11/RAD50/NBS1 complex, is one of key DNA damage response proteins. Increasing evidence suggests that its expression in cancer cells is critical to developing radioresistance; as such, MRE11 is an emerging marker for targeted radiosensitization strategies. Elevated MRE11 in tumor tissues has been associated with poor survival in patients undergoing radiotherapy, although in some cancer types, the opposite has been noted. The recent discovery of ionizing radiation-induced truncation of MRE11, which decreases its efficacy, may explain some of these paradoxical findings. The progress of research on the biological modulation of MRE11 expression is also discussed, with the potential application of small molecule or large molecule inhibitors of MRE11 for enhancing radiosensitivity. Current research has further highlighted both nuclease and non-nuclease activities of MRE11 in cancer cells treated with ionizing radiation, and differentiation between these is essential to verify the targeting effects of radiosensitizing agents. These updates clarify our understanding of how MRE11 expression may be utilized in future stratification of cancer patients for radiotherapy, and how it may be leveraged in shaping novel radiosensitization strategies.
Topics: Humans; MRE11 Homologue Protein; Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents
PubMed: 34022282
DOI: 10.1016/j.canlet.2021.05.013