-
Cancers Mar 2021Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological... (Review)
Review
Adjuvant treatment decisions for endometrial cancer (EC) are based on stage, the histological grade of differentiation, histological subtype, and few histopathological markers. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified four risk groups of EC patients using a combination of immunohistochemistry and mutation analysis: Polymerase Epsilon exonuclease domain mutated (POLE EDM), mismatch repair deficient (MMRd), p53 wild-type/copy-number-low (p53 wt), and p53-mutated/copy-number-high (p53 abn). Patients allocated to the POLE or abnormal p53 expression subtype are faced with a significantly altered outcome possibly requiring a modified adjuvant treatment decision. Within this review, we summarize the development of ProMisE, characterize the four molecular subtypes, and finally discuss its value in terms of a patient-tailored therapy in order to prevent significant under or overtreatment.
PubMed: 33806979
DOI: 10.3390/cancers13061478 -
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 -
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 -
Cancers Oct 2020Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons,... (Review)
Review
Radiotherapy using accelerated charged particles is rapidly growing worldwide. About 85% of the cancer patients receiving particle therapy are irradiated with protons, which have physical advantages compared to X-rays but a similar biological response. In addition to the ballistic advantages, heavy ions present specific radiobiological features that can make them attractive for treating radioresistant, hypoxic tumors. An ideal heavy ion should have lower toxicity in the entrance channel (normal tissue) and be exquisitely effective in the target region (tumor). Carbon ions have been chosen because they represent the best combination in this direction. Normal tissue toxicities and second cancer risk are similar to those observed in conventional radiotherapy. In the target region, they have increased relative biological effectiveness and a reduced oxygen enhancement ratio compared to X-rays. Some radiobiological properties of densely ionizing carbon ions are so distinct from X-rays and protons that they can be considered as a different "drug" in oncology, and may elicit favorable responses such as an increased immune response and reduced angiogenesis and metastatic potential. The radiobiological properties of carbon ions should guide patient selection and treatment protocols to achieve optimal clinical results.
PubMed: 33080914
DOI: 10.3390/cancers12103022