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Radiation Response Biomarkers for Individualised Cancer Treatments
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Radiation Response Biomarkers for Individualised Cancer Treatments

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Methodology, Drug and Device Discovery".

Deadline for manuscript submissions: closed (10 December 2020) | Viewed by 54918

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Christophe Badie

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Guest Editor
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon OX11 0RQ, UK
Interests: carcinogenesis; radiation biology; leukaemia; biomarkers
Dr. Eric Andreas Rutten

E-Mail
Guest Editor
Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxon OX11 0RQ, UK

Special Issue Information

Dear Colleagues,

Half of all patients diagnosed with cancer will undergo radiotherapy as part of their treatment. It is an important and effective tool in the arsenal to treat numerous solid tumours. However, even with precise planning, radiotherapy treatment outcome depends on multiple factors and can, in the process, damage healthy tissue with a degree of severity that is, until now, very difficult to predict. Moreover, radiotherapy induces cancer cell death by damaging their DNA and can also trigger the release of pro- and anti-inflammatory mediators.

Improving the precision of radiotherapy has long been the quest of cancer scientists and clinicians. Recent improvements in its precision have helped to deliver most of the dose to the tumour, sparing the surrounding healthy tissues, hence limiting radiation toxicity and long-term effects, such as therapy-related cancer caused by, amongst others, a combination of radiation-induced somatic mutations, modifications of the microenvironment, and inflammation. Biomarkers are essential for predicting and/or monitoring radiation exposure-associated effects. The aim of this Special Issue is to present an insight into the ongoing state-of-the-art research in the oncology radiation response biomarker field and its applications in the ever-evolving field of personalised medicine.

Biomarkers for cancer fall into two primary categories: diagnostic and predictive. In the case of radiotherapy for cancers, there is a need for both: (1) diagnosis of radiation response and subsequent effect on the cancer and (2) prediction of possible secondary cancers arising in the long term because of radiotherapy, e.g., acute myeloid leukaemia and sarcomas. Radiation biomarkers are thus necessary, not only for understanding the actual effects of treatment on a tumour, but also for monitoring the most effective total dose to the tumour and identifying mechanisms that may allow a tumour to resist radiation therapy, as well as identifying the risks to the patient stemming from the therapy. Ever-evolving technologies allow the detection and validation of new and emerging radiation biomarkers, whether genetic, epigenetic, cell-based, cell-free, or present in extracellular vesicles.

We welcome original scientific manuscripts (both clinical and research-based), reviews reporting novel findings in the field of radiation response, and biomarkers indicative of patient-tailored treatment and monitoring in both in vitro and in vivo systems, with a focus on research in human systems, as well as technical papers on new developments in protocols to study and validate these biomarkers.

Dr. Christophe Badie
Dr. Eric Andreas Rutten
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  •  Tumour
  •  Cancer treatment
  •  Ionizing radiation
  •  Biomarkers
  •  Personalised medicine
  •  Radiotherapy
  •  Radiosensitivity
  •  Immune system
  •  Inflammation
  •  Adverse normal tissue effects

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Published Papers (14 papers)

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Editorial

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5 pages, 197 KiB  
Editorial
Radiation Biomarkers: Silver Bullet, or Wild Goose Chase?
by Eric Andreas Rutten and Christophe Badie
J. Pers. Med. 2021, 11(7), 603; https://doi.org/10.3390/jpm11070603 - 25 Jun 2021
Cited by 5 | Viewed by 2445
Abstract
Humans have learned to harness the power of radiation for therapeutic ends, with 50% of all patients diagnosed with cancer undergoing radiotherapy as part of their treatment [...] Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)

Research

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22 pages, 3376 KiB  
Article
Telomere Length Dynamics and Chromosomal Instability for Predicting Individual Radiosensitivity and Risk via Machine Learning
by Jared J. Luxton, Miles J. McKenna, Aidan M. Lewis, Lynn E. Taylor, Sameer G. Jhavar, Gregory P. Swanson and Susan M. Bailey
J. Pers. Med. 2021, 11(3), 188; https://doi.org/10.3390/jpm11030188 - 8 Mar 2021
Cited by 13 | Viewed by 3732
Abstract
The ability to predict a cancer patient’s response to radiotherapy and risk of developing adverse late health effects would greatly improve personalized treatment regimens and individual outcomes. Telomeres represent a compelling biomarker of individual radiosensitivity and risk, as exposure can result in dysfunctional [...] Read more.
The ability to predict a cancer patient’s response to radiotherapy and risk of developing adverse late health effects would greatly improve personalized treatment regimens and individual outcomes. Telomeres represent a compelling biomarker of individual radiosensitivity and risk, as exposure can result in dysfunctional telomere pathologies that coincidentally overlap with many radiation-induced late effects, ranging from degenerative conditions like fibrosis and cardiovascular disease to proliferative pathologies like cancer. Here, telomere length was longitudinally assessed in a cohort of fifteen prostate cancer patients undergoing Intensity Modulated Radiation Therapy (IMRT) utilizing Telomere Fluorescence in situ Hybridization (Telo-FISH). To evaluate genome instability and enhance predictions for individual patient risk of secondary malignancy, chromosome aberrations were assessed utilizing directional Genomic Hybridization (dGH) for high-resolution inversion detection. We present the first implementation of individual telomere length data in a machine learning model, XGBoost, trained on pre-radiotherapy (baseline) and in vitro exposed (4 Gy γ-rays) telomere length measurements, to predict post radiotherapy telomeric outcomes, which together with chromosomal instability provide insight into individual radiosensitivity and risk for radiation-induced late effects. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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14 pages, 2763 KiB  
Article
Metabolic Profiles of Whole Serum and Serum-Derived Exosomes Are Different in Head and Neck Cancer Patients Treated by Radiotherapy
by Anna Wojakowska, Aneta Zebrowska, Agata Skowronek, Tomasz Rutkowski, Krzysztof Polanski, Piotr Widlak, Lukasz Marczak and Monika Pietrowska
J. Pers. Med. 2020, 10(4), 229; https://doi.org/10.3390/jpm10040229 - 13 Nov 2020
Cited by 33 | Viewed by 3460
Abstract
Background: In general, the serum metabolome reflects the patient’s body response to both disease state and implemented treatment. Though serum-derived exosomes are an emerging type of liquid biopsy, the metabolite content of these vesicles remains under researched. The aim of this pilot study [...] Read more.
Background: In general, the serum metabolome reflects the patient’s body response to both disease state and implemented treatment. Though serum-derived exosomes are an emerging type of liquid biopsy, the metabolite content of these vesicles remains under researched. The aim of this pilot study was to compare the metabolite profiles of the whole serum and serum-derived exosomes in the context of differences between cancer patients and healthy controls as well as patients’ response to radiotherapy (RT). Methods: Serum samples were collected from 10 healthy volunteers and 10 patients with head and neck cancer before and after RT. Metabolites extracted from serum and exosomes were analyzed by the gas chromatography–mass spectrometry (GC–MS). Results: An untargeted GC–MS-based approach identified 182 and 46 metabolites in serum and exosomes, respectively. Metabolites that differentiated cancer and control samples, either serum or exosomes, were associated with energy metabolism. Serum metabolites affected by RT were associated with the metabolism of amino acids, sugars, lipids, and nucleotides. Conclusions: cancer-related features of energy metabolism could be detected in both types of specimens. On the other hand, in contrast to RT-induced changes observed in serum metabolome, this pilot study did not reveal a specific radiation-related pattern of exosome metabolites. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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6 pages, 959 KiB  
Communication
Comparison of Clonogenic Survival Data Obtained by Pre- and Post-Irradiation Methods
by Takahiro Oike, Yuka Hirota, Narisa Dewi Maulany Darwis, Atsushi Shibata and Tatsuya Ohno
J. Pers. Med. 2020, 10(4), 171; https://doi.org/10.3390/jpm10040171 - 15 Oct 2020
Cited by 8 | Viewed by 3730
Abstract
Clonogenic assays are the gold standard to measure in vitro radiosensitivity, which use two cell plating methods, before or after irradiation (IR). However, the effect of the plating method on the experimental outcome remains unelucidated. By using common cancer cell lines, here we [...] Read more.
Clonogenic assays are the gold standard to measure in vitro radiosensitivity, which use two cell plating methods, before or after irradiation (IR). However, the effect of the plating method on the experimental outcome remains unelucidated. By using common cancer cell lines, here we demonstrate that pre-IR and post-IR plating methods have a negligible effect on the clonogenic assay-derived photon sensitivity as assessed by SF2, SF4, SF6, SF8, D10, or D50 (N.B. SFx indicates the survival at X Gy; Dx indicates the dose providing X% survival). These data provide important biological insight that supports inter-study comparison and integrated analysis of published clonogenic assay data regardless of the plating method used. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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14 pages, 1767 KiB  
Article
Radiation Biomarkers in Large Scale Human Health Effects Studies
by Jayne Moquet, Kai Rothkamm, Stephen Barnard and Elizabeth Ainsbury
J. Pers. Med. 2020, 10(4), 155; https://doi.org/10.3390/jpm10040155 - 3 Oct 2020
Cited by 6 | Viewed by 3108
Abstract
Following recent developments, the RENEB network (Running the European Network of biological dosimetry and physical retrospective dosimetry) is in an excellent position to carry out large scale molecular epidemiological studies of ionizing radiation effects, with validated expertise in the dicentric, fluorescent in situ [...] Read more.
Following recent developments, the RENEB network (Running the European Network of biological dosimetry and physical retrospective dosimetry) is in an excellent position to carry out large scale molecular epidemiological studies of ionizing radiation effects, with validated expertise in the dicentric, fluorescent in situ hybridization (FISH)-translocation, micronucleus, premature chromosome condensation, gamma-H2AX foci and gene expression assays. Large scale human health effects studies present complex challenges such as the practical aspects of sample logistics, assay costs, effort, effect modifiers and quality control/assurance measures. At Public Health England, the dicentric, automated micronucleus and gamma-H2AX radiation-induced foci assays have been tested for use in a large health effects study. The results of the study and the experience gained in carrying out such a large scale investigation provide valuable information that could help minimise random and systematic errors in biomarker data sets for health surveillance analyses going forward. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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12 pages, 1321 KiB  
Article
The Cytokinesis-Block Micronucleus Assay on Human Isolated Fresh and Cryopreserved Peripheral Blood Mononuclear Cells
by Simon Sioen, Karlien Cloet, Anne Vral and Ans Baeyens
J. Pers. Med. 2020, 10(3), 125; https://doi.org/10.3390/jpm10030125 - 14 Sep 2020
Cited by 13 | Viewed by 4634
Abstract
The cytokinesis-block micronucleus (CBMN) assay is a standardized method used for genotoxicity studies. Conventional whole blood cultures (WBC) are often used for this assay, although the assay can also be performed on isolated peripheral blood mononuclear cell (PBMC) cultures. However, the standardization of [...] Read more.
The cytokinesis-block micronucleus (CBMN) assay is a standardized method used for genotoxicity studies. Conventional whole blood cultures (WBC) are often used for this assay, although the assay can also be performed on isolated peripheral blood mononuclear cell (PBMC) cultures. However, the standardization of a protocol for the PBMC CBMN assay has not been investigated extensively. The aim of this study was to optimize a reliable CBMN assay protocol for fresh and cryopreserved peripheral blood mononuclear cells (PBMCS), and to compare micronuclei (MNi) results between WBC and PBMC cultures. The G0 CBMN assay was performed on whole blood, freshly isolated, and cryopreserved PBMCS from healthy human blood samples and five radiosensitive patient samples. Cells were exposed to 220 kV X-ray in vitro doses ranging from 0.5 to 2 Gy. The optimized PBMC CBMN assay showed adequate repeatability and small inter-individual variability. MNi values were significantly higher for WBC than for fresh PBMCS. Additionally, cryopreservation of PBMCS resulted in a significant increase of MNi values, while different cryopreservation times had no significant impact. In conclusion, our standardized CBMN assay on fresh and cryopreserved PBMCS can be used for genotoxicity studies, biological dosimetry, and radiosensitivity assessment. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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8 pages, 3186 KiB  
Communication
Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy
by Daijiro Kobayashi, Takahiro Oike, Kazutoshi Murata, Daisuke Irie, Yuka Hirota, Hiro Sato, Atsushi Shibata and Tatsuya Ohno
J. Pers. Med. 2020, 10(3), 110; https://doi.org/10.3390/jpm10030110 - 3 Sep 2020
Cited by 8 | Viewed by 3613
Abstract
Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy [...] Read more.
Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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9 pages, 1103 KiB  
Communication
Relative Biological Effectiveness of Carbon Ions for Head-and-Neck Squamous Cell Carcinomas According to Human Papillomavirus Status
by Naoto Osu, Daijiro Kobayashi, Katsuyuki Shirai, Atsushi Musha, Hiro Sato, Yuka Hirota, Atsushi Shibata, Takahiro Oike and Tatsuya Ohno
J. Pers. Med. 2020, 10(3), 71; https://doi.org/10.3390/jpm10030071 - 25 Jul 2020
Cited by 14 | Viewed by 3385
Abstract
Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions [...] Read more.
Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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Review

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31 pages, 889 KiB  
Review
Blood-Derived Biomarkers of Diagnosis, Prognosis and Therapy Response in Prostate Cancer Patients
by Katalin Balázs, Lilla Antal, Géza Sáfrány and Katalin Lumniczky
J. Pers. Med. 2021, 11(4), 296; https://doi.org/10.3390/jpm11040296 - 13 Apr 2021
Cited by 23 | Viewed by 4921
Abstract
Prostate cancer is among the most frequent cancers in men worldwide. Despite the fact that multiple therapeutic alternatives are available for its treatment, it is often discovered in an advanced stage as a metastatic disease. Prostate cancer screening is based on physical examination [...] Read more.
Prostate cancer is among the most frequent cancers in men worldwide. Despite the fact that multiple therapeutic alternatives are available for its treatment, it is often discovered in an advanced stage as a metastatic disease. Prostate cancer screening is based on physical examination of prostate size and prostate-specific antigen (PSA) level in the blood as well as biopsy in suspect cases. However, these markers often fail to correctly identify the presence of cancer, or their positivity might lead to overdiagnosis and consequent overtreatment of an otherwise silent non-progressing disease. Moreover, these markers have very limited if any predictive value regarding therapy response or individual risk for therapy-related toxicities. Therefore, novel, optimally liquid biopsy-based (blood-derived) markers or marker panels are needed, which have better prognostic and predictive value than the ones currently used in the everyday routine. In this review the role of circulating tumour cells, extracellular vesicles and their microRNA content, as well as cellular and soluble immunological and inflammation- related blood markers for prostate cancer diagnosis, prognosis and prediction of therapy response is discussed. A special emphasis is placed on markers predicting response to radiotherapy and radiotherapy-related late side effects. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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15 pages, 735 KiB  
Review
Radiation Response in the Tumour Microenvironment: Predictive Biomarkers and Future Perspectives
by Niall M. Byrne, Prajakta Tambe and Jonathan A. Coulter
J. Pers. Med. 2021, 11(1), 53; https://doi.org/10.3390/jpm11010053 - 16 Jan 2021
Cited by 17 | Viewed by 3374
Abstract
Radiotherapy (RT) is a primary treatment modality for a number of cancers, offering potentially curative outcomes. Despite its success, tumour cells can become resistant to RT, leading to disease recurrence. Components of the tumour microenvironment (TME) likely play an integral role in managing [...] Read more.
Radiotherapy (RT) is a primary treatment modality for a number of cancers, offering potentially curative outcomes. Despite its success, tumour cells can become resistant to RT, leading to disease recurrence. Components of the tumour microenvironment (TME) likely play an integral role in managing RT success or failure including infiltrating immune cells, the tumour vasculature and stroma. Furthermore, genomic profiling of the TME could identify predictive biomarkers or gene signatures indicative of RT response. In this review, we will discuss proposed mechanisms of radioresistance within the TME, biomarkers that may predict RT outcomes, and future perspectives on radiation treatment in the era of personalised medicine. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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9 pages, 233 KiB  
Review
Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: Protocol for a Systematic Review
by Anne Dietz, Maria Gomolka, Simone Moertl and Prabal Subedi
J. Pers. Med. 2021, 11(1), 3; https://doi.org/10.3390/jpm11010003 - 22 Dec 2020
Cited by 6 | Viewed by 2990
Abstract
Background: Radiosensitivity is a significantly enhanced reaction of cells, tissues, organs or organisms to ionizing radiation (IR). During radiotherapy, surrounding normal tissue radiosensitivity often limits the radiation dose that can be applied to the tumour, resulting in suboptimal tumour control or adverse effects [...] Read more.
Background: Radiosensitivity is a significantly enhanced reaction of cells, tissues, organs or organisms to ionizing radiation (IR). During radiotherapy, surrounding normal tissue radiosensitivity often limits the radiation dose that can be applied to the tumour, resulting in suboptimal tumour control or adverse effects on the life quality of survivors. Predicting radiosensitivity is a component of personalized medicine, which will help medical professionals allocate radiation therapy decisions for effective tumour treatment. So far, there are no reviews of the current literature that explore the relationship between proteomic changes after IR exposure and normal tissue radiosensitivity systematically. Objectives: The main objective of this protocol is to specify the search and evaluation strategy for a forthcoming systematic review (SR) dealing with the effects of in vivo and in vitro IR exposure on the proteome of human normal tissue with focus on radiosensitivity. Methods: The SR framework has been developed following the guidelines established in the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Handbook for Conducting a Literature-Based Health Assessment, which provides a standardised methodology to implement the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health assessments. The protocol will be registered in PROSPERO, an open source protocol registration system, to guarantee transparency. Eligibility criteria: Only experimental studies, in vivo and in vitro, investigating effects of ionizing radiation on the proteome of human normal tissue correlated with radio sensitivity will be included. Eligible studies will include English peer reviewed articles with publication dates from 2011–2020 which are sources of primary data. Information sources: The search strings will be applied to the scientific literature databases PubMed and Web of Science. The reference lists of included studies will also be manually searched. Data extraction and results: Data will be extracted according to a pre-defined modality and compiled in a narrative report following guidelines presented as a “Synthesis without Meta-analyses” method. Risk of bias: The risk of bias will be assessed based on the NTP/OHAT risk of bias rating tool for human and animal studies (OHAT 2019). Level of evidence rating: A comprehensive assessment of the quality of evidence for both in vivo and in vitro studies will be followed, by assigning a confidence rating to the literature. This is followed by translation into a rating on the level of evidence (high, moderate, low, or inadequate) regarding the research question. Registration: PROSPERO Submission ID 220064. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
36 pages, 370 KiB  
Review
Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review
by Volodymyr Vinnikov, Manoor Prakash Hande, Ruth Wilkins, Andrzej Wojcik, Eduardo Zubizarreta and Oleg Belyakov
J. Pers. Med. 2020, 10(4), 285; https://doi.org/10.3390/jpm10040285 - 16 Dec 2020
Cited by 16 | Viewed by 3942
Abstract
A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction [...] Read more.
A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4–6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
16 pages, 319 KiB  
Review
Markers Useful in Monitoring Radiation-Induced Lung Injury in Lung Cancer Patients: A Review
by Mariola Śliwińska-Mossoń, Katarzyna Wadowska, Łukasz Trembecki and Iwona Bil-Lula
J. Pers. Med. 2020, 10(3), 72; https://doi.org/10.3390/jpm10030072 - 26 Jul 2020
Cited by 15 | Viewed by 4849
Abstract
In 2018, lung cancer was the most common cancer and the most common cause of cancer death, accounting for a 1.76 million deaths. Radiotherapy (RT) is a widely used and effective non-surgical cancer treatment that induces remission in, and even cures, patients with [...] Read more.
In 2018, lung cancer was the most common cancer and the most common cause of cancer death, accounting for a 1.76 million deaths. Radiotherapy (RT) is a widely used and effective non-surgical cancer treatment that induces remission in, and even cures, patients with lung cancer. However, RT faces some restrictions linked to the radioresistance and treatment toxicity, manifesting in radiation-induced lung injury (RILI). About 30–40% of lung cancer patients will develop RILI, which next to the local recurrence and distant metastasis is a substantial challenge to the successful management of lung cancer treatment. These data indicate an urgent need of looking for novel, precise biomarkers of individual response and risk of side effects in the course of RT. The aim of this review was to summarize both preclinical and clinical approaches in RILI monitoring that could be brought into clinical practice. Next to transforming growth factor-β1 (TGFβ1) that was reported as one of the most important growth factors expressed in the tissues after ionizing radiation (IR), there is a group of novel, potential biomarkers—microRNAs—that may be used as predictive biomarkers in therapy response and disease prognosis. Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)

Other

26 pages, 1044 KiB  
Systematic Review
Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: A Systematic Review
by Prabal Subedi, Maria Gomolka, Simone Moertl and Anne Dietz
J. Pers. Med. 2021, 11(2), 140; https://doi.org/10.3390/jpm11020140 - 19 Feb 2021
Cited by 18 | Viewed by 4526
Abstract
Background and objectives: Exposure to ionizing radiation (IR) has increased immensely over the past years, owing to diagnostic and therapeutic reasons. However, certain radiosensitive individuals show toxic enhanced reaction to IR, and it is necessary to specifically protect them from unwanted exposure. [...] Read more.
Background and objectives: Exposure to ionizing radiation (IR) has increased immensely over the past years, owing to diagnostic and therapeutic reasons. However, certain radiosensitive individuals show toxic enhanced reaction to IR, and it is necessary to specifically protect them from unwanted exposure. Although predicting radiosensitivity is the way forward in the field of personalised medicine, there is limited information on the potential biomarkers. The aim of this systematic review is to identify evidence from a range of literature in order to present the status quo of our knowledge of IR-induced changes in protein expression in normal tissues, which can be correlated to radiosensitivity. Methods: Studies were searched in NCBI Pubmed and in ISI Web of Science databases and field experts were consulted for relevant studies. Primary peer-reviewed studies in English language within the time-frame of 2011 to 2020 were considered. Human non-tumour tissues and human-derived non-tumour model systems that have been exposed to IR were considered if they reported changes in protein levels, which could be correlated to radiosensitivity. At least two reviewers screened the titles, keywords, and abstracts of the studies against the eligibility criteria at the first phase and full texts of potential studies at the second phase. Similarly, at least two reviewers manually extracted the data and accessed the risk of bias (National Toxicology Program/Office for Health Assessment and Translation—NTP/OHAT) for the included studies. Finally, the data were synthesised narratively in accordance to synthesis without meta analyses (SWiM) method. Results: In total, 28 studies were included in this review. Most of the records (16) demonstrated increased residual DNA damage in radiosensitive individuals compared to normo-sensitive individuals based on γH2AX and TP53BP1. Overall, 15 studies included proteins other than DNA repair foci, of which five proteins were selected, Vascular endothelial growth factor (VEGF), Caspase 3, p16INK4A (Cyclin-dependent kinase inhibitor 2A, CDKN2A), Interleukin-6, and Interleukin-1β, that were connected to radiosensitivity in normal tissue and were reported at least in two independent studies. Conclusions and implication of key findings: A majority of studies used repair foci as a tool to predict radiosensitivity. However, its correlation to outcome parameters such as repair deficient cell lines and patients, as well as an association to moderate and severe clinical radiation reactions, still remain contradictory. When IR-induced proteins reported in at least two studies were considered, a protein network was discovered, which provides a direction for further studies to elucidate the mechanisms of radiosensitivity. Although the identification of only a few of the commonly reported proteins might raise a concern, this could be because (i) our eligibility criteria were strict and (ii) radiosensitivity is influenced by multiple factors. Registration: PROSPERO (CRD42020220064). Full article
(This article belongs to the Special Issue Radiation Response Biomarkers for Individualised Cancer Treatments)
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