Authors: Claire Vanpouille-Box

Topics: Humans; Neoplasms; Radiobiology

PubMed: 34112189
DOI: 10.1186/s12967-021-02928-w

Review

Authors: Zachary S Morris, Andrew Z Wang, Susan J Knox...

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

Authors: Piyawan Chailapakul, Takamitsu A Kato

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

Authors: Daniela L Stricklin, Jama VanHorne-Sealy, Carmen I Rios...

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

Review

Authors: Mary Helen Barcellos-Hoff

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

Review

Authors: Walter Tinganelli, Marco Durante

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

Review

Authors: Constantin Tuleasca, Manjul Tripathi, Daniele Starnoni...

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

Review

Authors: Reem Ahmad, Amelia Barcellini, Kilian Baumann...

Particle therapy (PT) represents a significant advancement in cancer treatment, precisely targeting tumor cells while sparing surrounding healthy tissues thanks to the unique depth-dose profiles of the charged particles. Furthermore, their linear energy transfer and relative biological effectiveness enhance their capability to treat radioresistant tumors, including hypoxic ones. Over the years, extensive research has paved the way for PT's clinical application, and current efforts aim to refine its efficacy and precision, minimizing the toxicities. In this regard, radiobiology research is evolving toward integrating biotechnology to advance drug discovery and radiation therapy optimization. This shift from basic radiobiology to understanding the molecular mechanisms of PT aims to expand the therapeutic window through innovative dose delivery regimens and combined therapy approaches. This review, written by over 30 contributors from various countries, provides a comprehensive look at key research areas and new developments in PT radiobiology, emphasizing the innovations and techniques transforming the field, ranging from the radiobiology of new irradiation modalities to multimodal radiation therapy and modeling efforts. We highlight both advancements and knowledge gaps, with the aim of improving the understanding and application of PT in oncology.

PubMed: 39258166
DOI: 10.1016/j.ijpt.2024.100626

Authors: David G Kirsch, Max Diehn, Aparna H Kesarwala...

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

Authors: Daniel K Ebner, Takashi Shimokawa, Walter Tinganelli...

Topics: Radiobiology; Linear Energy Transfer

PubMed: 37050959
DOI: 10.3389/fpubh.2023.1181656