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Journal of Translational Medicine Jun 2021
Topics: Humans; Neoplasms; Radiobiology
PubMed: 34112189
DOI: 10.1186/s12967-021-02928-w -
Seminars in Radiation Oncology Jan 2021Radiopharmaceutical therapy or targeted radionuclide therapy (TRT) is a well-established class of cancer therapeutics that includes a growing number of FDA-approved... (Review)
Review
Radiopharmaceutical therapy or targeted radionuclide therapy (TRT) is a well-established class of cancer therapeutics that includes a growing number of FDA-approved drugs and a promising pipeline of experimental therapeutics. Radiobiology is fundamental to a mechanistic understanding of the therapeutic capacity of these agents and their potential toxicities. However, the field of radiobiology has historically focused on external beam radiation. Critical differences exist between TRT and external beam radiotherapy with respect to dosimetry, dose rate, linear energy transfer, duration of treatment delivery, fractionation, range, and target volume. These distinctions simultaneously make it difficult to extrapolate from the radiobiology of external beam radiation to that of TRT and pose considerable challenges for preclinical and clinical studies investigating TRT. Here, we discuss these challenges and explore the current understanding of the radiobiology of radiopharmaceuticals.
Topics: Humans; Linear Energy Transfer; Neoplasms; Radiobiology; Radiometry; Radiopharmaceuticals
PubMed: 33246632
DOI: 10.1016/j.semradonc.2020.07.002 -
International Journal of Molecular... Dec 2022The Special Issue, entitled "From basic radiobiology to translational radiotherapy", highlights recent advances in basic radiobiology and the potential to improve...
The Special Issue, entitled "From basic radiobiology to translational radiotherapy", highlights recent advances in basic radiobiology and the potential to improve radiotherapy in translational research [...].
Topics: Radiobiology; Radiation Oncology; Radiotherapy
PubMed: 36555542
DOI: 10.3390/ijms232415902 -
Progress in Brain Research 2022New understandings of the biology of radiosurgery are considered. Differences from the radiobiology of fractionated radiotherapy are outlined. It is noted DNA damage...
New understandings of the biology of radiosurgery are considered. Differences from the radiobiology of fractionated radiotherapy are outlined. It is noted DNA damage alone is insufficient to account for the tissue changes which occur. Changes in blood vessels and immunological mechanisms are also involved. Tissue repair is more rapid than previously thought so that dose rate (the rate of delivery of radiation to the tissues) has been seen to be more important. The value of fractionation is examined. The effect of radiosurgery on normal brain (so called functional radiosurgery) is considered. The desired effects may be achieved by a focal stable destruction of brain from a high radiation dose. They may also be achieved using a lower dose which acts through the mechanism known as radiosurgical neuromodulation.
Topics: Brain; Dose Fractionation, Radiation; Humans; Radiobiology; Radiosurgery
PubMed: 35074083
DOI: 10.1016/bs.pbr.2021.10.024 -
Medical Physics Nov 2018Radiogenomics is the study of genomic changes that underlie the radioresponse of normal and tumor tissues. And while this is generally regarded as a whole genome... (Review)
Review
PURPOSE
Radiogenomics is the study of genomic changes that underlie the radioresponse of normal and tumor tissues. And while this is generally regarded as a whole genome approach, one must keep in mind the impact of single gene biology on radioresponse, (ataxia telangiectasia, Nijmegen breakage syndrome).
METHODS
This review begins with the association of single nucleotide polymorphisms in the DNA with adverse normal tissue events to the prediction of therapeutic outcome after radiotherapy. From there it covers transcriptome (protein coding RNA transcripts) analysis, which is where the greatest understanding of the molecular signaling responsible for the radioresponse of tumors and normal tissues is known. Non-protein coding RNA transcripts (miRNA, lncRNA), transcribed from what was once thought of as junk DNA, are now known to be negative regulators of the transcription of mRNA by multiple mechanisms. miRNA can act as tumor suppressors or oncogenes regulating a diverse range of cellular processes that drive radioresponse and biosignatures that predict outcome after radiotherapy are described.
RESULTS
Biological signatures that explain differences in radioresponse based upon cell type, biological signatures that predict surviving fraction at 2 Gy and signatures that identify hypoxia have been described. The omics analysis of the response of mammalian cells to charged particle, predominantly proton and carbon ions, is less mature than that seen with low LET radiation exposures. However, there appear to be responses after charged particle exposure that parallel the responses seem with low LET exposures. This commonality of response is centered around the downstream signaling of p53. There are also novel omics responses to charged particles that help explain the response of tumors to charged particle exposures. For instance, signaling pathways associated with angiogenesis, vasculogenesis, migration and invasion appear to be downregulated in a number of cell types when exposed to charged particles. This response supports both in vitro and in vivo data suggesting that tumors exposed to charged particles are less invasive, unlike the response of tumors to low LET exposures. Profoundly lacking for low LET and charged particle exposures are predictive or prognostic signatures of radioresponse or tumor physiology affecting radioresponse that have been validated in prospective clinical trials. For example, the identification of low LET tumor radioresistance could be used as a marker of patient eligibility for carbon therapy. Tissue specific signatures, or accurate imaging of hypoxic regions, could be used for charged particle selection to overcome hypoxia per se, or could be used to prescribe a high LET therapeutic boost to a hypoxic region of a tumor.
CONCLUSIONS
Integrating radiogenomics into radiation oncology has the potential to personalize an already precise form of cancer therapy.
Topics: Genomics; Humans; Neoplasms; Radiobiology; Transcription, Genetic
PubMed: 30421807
DOI: 10.1002/mp.13064 -
Seminars in Cancer Biology Nov 2022Ionizing radiation is a pillar of cancer therapy that is deployed in more than half of all malignancies. The therapeutic effect of radiation is attributed to induction... (Review)
Review
Ionizing radiation is a pillar of cancer therapy that is deployed in more than half of all malignancies. The therapeutic effect of radiation is attributed to induction of DNA damage that kills cancers cells, but radiation also affects signaling that alters the composition of the tumor microenvironment by activating transforming growth factor β (TGFβ). TGFβ is a ubiquitously expressed cytokine that acts as biological lynchpin to orchestrate phenotypes, the stroma, and immunity in normal tissue; these activities are subverted in cancer to promote malignancy, a permissive tumor microenvironment and immune evasion. The radiobiology of TGFβ unites targets at the forefront of oncology-the DNA damage response and immunotherapy. The cancer cell intrinsic and extrinsic network of TGFβ responses in the irradiated tumor form a barrier to both genotoxic treatments and immunotherapy response. Here, we focus on the mechanisms by which radiation induces TGFβ activation, how TGFβ regulates DNA repair, and the dynamic regulation of the tumor immune microenvironment that together oppose effective cancer therapy. Strategies to inhibit TGFβ exploit fundamental radiobiology that may be the missing link to deploying TGFβ inhibitors for optimal patient benefit from cancer treatment.
Topics: Humans; Transforming Growth Factor beta; Radiobiology; DNA Damage; Signal Transduction; Neoplasms; Tumor Microenvironment
PubMed: 35122974
DOI: 10.1016/j.semcancer.2022.02.001 -
Cancer Letters Jul 2023Radiotherapy (RT) is one of the key modalities for cancer treatment, and more than 70% of tumor patients will receive RT during the course of their disease. Particle... (Review)
Review
Radiotherapy (RT) is one of the key modalities for cancer treatment, and more than 70% of tumor patients will receive RT during the course of their disease. Particle radiotherapy, such as proton radiotherapy, carbon-ion radiotherapy (CIRT) and boron neutron capture therapy (BNCT), is currently available for the treatment of patients Immunotherapy combined with photon RT has been successfully used in the clinic. The effect of immunotherapy combined with particle RT is an area of interest. However, the molecular mechanisms underlying the effects of combined immunotherapy and particle RT remain largely unknown. In this review, we summarize the properties of different types of particle RT and the mechanisms underlying their radiobiological effects. Additionally, we compared the main molecular players in photon RT and particle RT and the mechanisms involved the RT-mediated immune response.
Topics: Humans; Radioimmunotherapy; Boron Neutron Capture Therapy; Neoplasms; Radiation Oncology; Radiobiology
PubMed: 37331583
DOI: 10.1016/j.canlet.2023.216268 -
Neurology India 2023Stereotactic radiosurgery (SRS) is a precise focusing of radiation to a targeted point or larger area of tissue. With advances in technology, the radiobiological... (Review)
Review
Stereotactic radiosurgery (SRS) is a precise focusing of radiation to a targeted point or larger area of tissue. With advances in technology, the radiobiological understanding of this modality has trailed behind. Although found effective in both short- and long-term follow-up, there are ongoing evolution and controversial topics such as dosing pattern, dose per fraction in hypo-fractionnated regimens, inter-fraction interval, and so on. Radiobiology of radiosurgery is not a mere extension of conventional fractionation radiotherapy, but it demands further evaluation of the dose calculation on the linear linear-quadratic model, which has also its limits, biologically effective dose, and radiosensitivity of the normal and target tissue. Further research is undergoing to understand this somewhat controversial topic of radiosurgery better.
Topics: Humans; Radiosurgery; Neurosurgeons; Radiobiology; Dose Fractionation, Radiation
PubMed: 37026330
DOI: 10.4103/0028-3886.373637 -
Radiation Research May 2021As the U.S. prepares for the possibility of a radiological or nuclear incident, or anticipated lunar and Mars missions, the exposure of individuals to neutron radiation...
As the U.S. prepares for the possibility of a radiological or nuclear incident, or anticipated lunar and Mars missions, the exposure of individuals to neutron radiation must be considered. More information is needed on how to determine the neutron dose to better estimate the true biological effects of neutrons and mixed-field (i.e., neutron and photon) radiation exposures. While exposure to gamma-ray radiation will cause significant health issues, the addition of neutrons will likely exacerbate the biological effects already anticipated after radiation exposure. To begin to understand the issues and knowledge gaps in these areas, the National Institute of Allergy and Infectious Diseases (NIAID), Radiation Nuclear Countermeasures Program (RNCP), Department of Defense (DoD), Defense Threat Reduction Agency (DTRA), and National Aeronautics and Space Administration (NASA) formed an inter-agency working group to host a Neutron Radiobiology and Dosimetry Workshop on March 7, 2019 in Rockville, MD. Stakeholder interests were clearly positioned, given the differences in the missions of each agency. An overview of neutron dosimetry and neutron radiobiology was included, as well as a historical overview of neutron exposure research. In addition, current research in the fields of biodosimetry and diagnostics, medical countermeasures (MCMs) and treatment, long-term health effects, and computational studies were presented and discussed.
Topics: Gamma Rays; Humans; Neutrons; Radiobiology; Radiometry
PubMed: 33587743
DOI: 10.1667/RADE-20-00213.1 -
Journal of the National Cancer Institute Apr 2018Innovation and progress in radiation oncology depend on discovery and insights realized through research in radiation biology. Radiobiology research has led to...
Innovation and progress in radiation oncology depend on discovery and insights realized through research in radiation biology. Radiobiology research has led to fundamental scientific insights, from the discovery of stem/progenitor cells to the definition of signal transduction pathways activated by ionizing radiation that are now recognized as integral to the DNA damage response (DDR). Radiobiological discoveries are guiding clinical trials that test radiation therapy combined with inhibitors of the DDR kinases DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and immune or cell cycle checkpoint inhibitors. To maintain scientific and clinical relevance, the field of radiation biology must overcome challenges in research workforce, training, and funding. The National Cancer Institute convened a workshop to discuss the role of radiobiology research and radiation biologists in the future scientific enterprise. Here, we review the discussions of current radiation oncology research approaches and areas of scientific focus considered important for rapid progress in radiation sciences and the continued contribution of radiobiology to radiation oncology and the broader biomedical research community.
Topics: Animals; Biomedical Research; Humans; Neoplasms; Radiobiology; Signal Transduction
PubMed: 29126306
DOI: 10.1093/jnci/djx231