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Journal of Applied Clinical Medical... Dec 2022In recent decades, the principal goals of participants in the field of radiation biologists have included defining dose thresholds for cancer and non-cancer endpoints to... (Review)
Review
In recent decades, the principal goals of participants in the field of radiation biologists have included defining dose thresholds for cancer and non-cancer endpoints to be used by regulators, clinicians and industry, as well as informing on best practice radiation utilization and protection applications. Importantly, much of this work has required an intimate relationship between "bench" radiation biology scientists and their target audiences (such as physicists, medical practitioners and epidemiologists) in order to ensure that the requisite gaps in knowledge are adequately addressed. However, despite the growing risk for public exposure to higher-than-background levels of radiation, e.g. from long-distance travel, the increasing use of ionizing radiation during medical procedures, the threat from geopolitical instability, and so forth, there has been a dramatic decline in the number of qualified radiation biologists in the U.S. Contributing factors are thought to include the loss of applicable training programs, loss of jobs, and declining opportunities for advancement. This report was undertaken in order to begin addressing this situation since inaction may threaten the viability of radiation biology as a scientific discipline.
Topics: Humans; United States; Workforce; Radiobiology; Physicians
PubMed: 36705246
DOI: 10.1002/acm2.13743 -
Biology Oct 2022The present paper reviews a non-targeted effect in radiobiology known as the Radiation-Induced Rescue Effect (RIRE) and insights gained from previous microbeam... (Review)
Review
The present paper reviews a non-targeted effect in radiobiology known as the Radiation-Induced Rescue Effect (RIRE) and insights gained from previous microbeam experiments on RIRE. RIRE describes the mitigation of radiobiological effects in targeted irradiated cells after they receive feedback signals from co-cultured non-irradiated bystander cells, or from the medium previously conditioning those co-cultured non-irradiated bystander cells. RIRE has established or has the potential of establishing relationships with other non-traditional new developments in the fields of radiobiology, including Radiation-Induced Bystander Effect (RIBE), Radiation-Induced Field Size Effect (RIFSE) and ultra-high dose rate (FLASH) effect, which are explained. The paper first introduces RIRE, summarizes previous findings, and surveys the mechanisms proposed for observations. Unique opportunities offered by microbeam irradiations for RIRE research and some previous microbeam studies on RIRE are then described. Some thoughts on future priorities and directions of research on RIRE exploiting unique features of microbeam radiations are presented in the last section.
PubMed: 36358251
DOI: 10.3390/biology11111548 -
International Journal of Molecular... Mar 2022The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs.... (Review)
Review
The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.
Topics: Dose Fractionation, Radiation; Humans; Neoplasms; Photons; Radiation Oncology; Radiobiology; Radiotherapy
PubMed: 35328787
DOI: 10.3390/ijms23063366 -
Cancers Sep 2021Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8-10% of all intracranial tumors and are the most common tumors of the... (Review)
Review
Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8-10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance.
PubMed: 34572805
DOI: 10.3390/cancers13184575 -
Physics in Medicine and Biology Aug 2017Advances in patient-specific information and biotechnology have contributed to a new era of computational medicine. Radiogenomics has emerged as a new field that... (Review)
Review
Advances in patient-specific information and biotechnology have contributed to a new era of computational medicine. Radiogenomics has emerged as a new field that investigates the role of genetics in treatment response to radiation therapy. Radiation oncology is currently attempting to embrace these recent advances and add to its rich history by maintaining its prominent role as a quantitative leader in oncologic response modeling. Here, we provide an overview of radiogenomics starting with genotyping, data aggregation, and application of different modeling approaches based on modifying traditional radiobiological methods or application of advanced machine learning techniques. We highlight the current status and potential for this new field to reshape the landscape of outcome modeling in radiotherapy and drive future advances in computational oncology.
Topics: Genomics; Humans; Models, Biological; Neoplasms; Radiobiology; Treatment Outcome
PubMed: 28657906
DOI: 10.1088/1361-6560/aa7c55 -
Medical Physics Jun 2022While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As... (Review)
Review
While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous dosimetry, 3D treatment planning, volumetric image guidance, or motion management, may play a major role in defining how to use, or whether to use, FLASH radiotherapy. Given the extended time frame for patients to experience late effects, we recommend moving deliberately but cautiously forward toward clinical trials. In this paper, we review the state of quality assurance and safety systems in FLASH, identify critical pre-clinical data points that need to be defined, and suggest how lessons learned from previous technological advancements will help us close the gaps and build a successful path to evidence-driven FLASH implementation.
Topics: Clinical Trials as Topic; Credentialing; Humans; Proton Therapy; Radiation Oncology; Radiobiology; Radiotherapy Dosage
PubMed: 35366339
DOI: 10.1002/mp.15623 -
Current Oncology (Toronto, Ont.) Feb 2022Even though it is only the 6th most common malignancy at the modal level, head and neck cancers are distinguished by a considerable treatment failure rate, especially by... (Review)
Review
Even though it is only the 6th most common malignancy at the modal level, head and neck cancers are distinguished by a considerable treatment failure rate, especially by locoregional recurrences, the intrinsic tumor radioresistance being one of the causes of this phenomenon. The efforts of radiobiological research of these cancers are oriented towards the identification of biomarkers associated with radioresistance and radiosensitivity in order to modulate the treatment so that the therapeutic benefit is maximum. Micro-RNAs (miRNAs, miRs), small single-stranded non-coding RNA molecules are currently being extensively evaluated as potential biomarkers in numerous diseases, including cancer. The evaluation of the potential of miRNAs to modulate or predict radiosensitivity or radioresistance, to anticipate the risk of recurrence and metastasis, and to differentiate different tumor subtypes is based on multiple mechanisms by which mRNAs control proliferation and apoptosis and interact with cell cycle phases or act as oncogenes with the potential to influence invasion promotion or tumor suppression. A refinement of radiosensitivity based on miRNAs with clinical and radiobiological application in head and neck cancers can lead to a personalization of radiotherapy. Thus, a miRNA signature can anticipate the risk of toxicity associated with chemoradiation, the possibility of obtaining locoregional control after treatment, and the recurrence and distant metastasis risk. The potential of miRNAs as an intrinsic predictor of sensitivity to chemotherapy may also guide the therapeutic decision toward choosing an escalation or de-escalation of concurrent or sequential systemic treatment. The choice of the irradiated dose, the fractional dose, the fractionation scheme, and the refining of the dose-volume constraints depending on the radiosensitivity of each tissue type estimated on a case-by-case basis by miRNAs profile are possible concepts for the future radiotherapy and radiobiology of head and neck cancers.
Topics: Head and Neck Neoplasms; Humans; MicroRNAs; Neoplasm Recurrence, Local; Radiation Tolerance; Radiobiology
PubMed: 35200568
DOI: 10.3390/curroncol29020069 -
OncoTargets and Therapy 2020Disulfiram (DSF), also known as "Antabuse", has been widely used in clinical practice to treat alcoholism. In the past decades, both in vivo and in vitro experiments... (Review)
Review
Disulfiram (DSF), also known as "Antabuse", has been widely used in clinical practice to treat alcoholism. In the past decades, both in vivo and in vitro experiments showed that DSF has strong anti-cancer activity, there were some clinical studies indicated the administration of this drug was associated with favorable survival in breast cancer. It is also evident that DSF has a radioprotective effect on normal cells and could be utilized during the course of radiation therapy. Moreover, increasing evidences demonstrated the role of DSF in enhancing the radiosensitivity of tumor cells in number of alternative mechanisms. Recent studies have also elaborated the anticancer mechanism of DSF in tumor cells. This review summarizes the anticancer activity of DSF both in preclinical studies and clinical trials, focuses on the advances of this drug in radiobiology and the treatment of breast cancer, and reveals the promising of repurposing DSF as a novel radiosensitizer and radioprotector in further clinical trials.
PubMed: 33116623
DOI: 10.2147/OTT.S271532 -
Reports of Practical Oncology and... 2017Recent advances in the technology of radiotherapy have enabled the development of new therapeutic modalities that deliver radiation with very high accuracy, reduced... (Review)
Review
Recent advances in the technology of radiotherapy have enabled the development of new therapeutic modalities that deliver radiation with very high accuracy, reduced margins and high dose conformation, allowing the reduction of healthy tissue irradiated and therefore minimizing the risk of toxicity. The next step was to increase the total tumor dose using conventional fractionation (which remains the best way to relatively radioprotect healthy tissues when large volumes are treated) or to use new fractionation schemes with greater biological effectiveness. Based on the experience gained in radiosurgery, the latter way was chosen for small and well-defined tumors in the body. Stereotactic body radiotherapy delivers high doses of radiation to small and well-defined targets in an extreme hypofractionated (and accelerated) scheme with a very high biological effectiveness obtaining very good initial clinical results in terms of local tumor control and acceptable rate of late complications. In fact, we realize a posteriori that it was not feasible to administer such biologically equivalent dose in a conventional fractionation because the treatment could last several months. So far, these new therapeutic modalities have been developed due to technologic advances in image guidance and treatment delivery but without a solid biological basis. It is the role of traditional radiobiology (and molecular radiobiology) to explain the effects of high doses of ionizing radiation on tumor and normal tissues. Only through a better understanding of how high doses of ionizing radiation act, clinicians will know exactly what we do, allowing us in the future to refine our treatments. This article attempts to describe through simple and understandable concepts the known aspects of the biological action of high doses of radiation on tumor and normal tissues, but it is clear that we need much more basic research to better understand the biology of high doses of radiation.
PubMed: 28490978
DOI: 10.1016/j.rpor.2017.02.010 -
International Journal of Radiation... 2022This article will briefly review the origins and evolution of functional genomics, first describing the experimental technology, and then some of the approaches applied...
PURPOSE
This article will briefly review the origins and evolution of functional genomics, first describing the experimental technology, and then some of the approaches applied to data analysis and visualization. It will emphasize application of functional genomics to radiation biology, using examples from the author's work to illustrate several key types of analysis. It concludes with a look at non-coding RNA, alternative reading of the genome, and single-cell transcriptomics, some of the innovative areas that may help to shape future research in radiation biology and oncology.
CONCLUSIONS
Transcriptomic approaches have provided insight into many areas of radiation biology and medicine, and innovations in technology and data analysis approaches promise continued contributions to radiation science in the future.
Topics: Genomics; Radiobiology; Transcriptome
PubMed: 34586968
DOI: 10.1080/09553002.2021.1987562