Special Issue "The Role of Radiation in Cancer Treatment: New Insights towards Personalized Therapies"

A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (15 December 2021).

Special Issue Editors

Dr. Luigi Minafra
E-Mail Website
Guest Editor
National Research Council (CNR), Institute of Bioimaging and Molecular Physiology (IBFM), Cefalù, PA, Italy
Interests: radiobiology; cancer; radiosensitizing agents; cell and molecular biology; genomics; gene signatures; biomarkers; human genetics
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Paolo Cammarata
E-Mail Website
Guest Editor
National Research Council (CNR), Institute of Bioimaging and Molecular Physiology (IBFM), Cefalù, PA, Italy
Interests: radiobiology; cancer; radiosensitizing agents; cell biology; animal science; preclinical imaging; micro pet; biomarkers; proteomics
Special Issues, Collections and Topics in MDPI journals
Dr. Marco Calvaruso
E-Mail Website
Guest Editor
National Research Council (CNR), Institute of Bioimaging and Molecular Physiology (IBFM), Cefalù, PA, Italy
Interests: space biology; radiobiology; cancer biology; radiosensitizing agents; cell and molecular biology; tumor immunology; human pathology, immunotherapy; biomarkers; target therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

At present, radiation therapy (RT) remains an essential component of multimodality approaches for the treatment of many types of cancer, and one of the most effective cancer therapies. Approximately, the 50–60% of all cancer patients will receive RT through several modalities, such as internal or external RT, either alone or in combination with other treatment regimens (i.e., surgery or chemotherapy).

Over the last decade, the technological development of RT has led to the ability to deliver with high precision a specific dose of ionizing radiation (IR) on the tumor target, also thanks to the use of hadrons such as protons and carbon ions, thus limiting the damage to healthy tissues.

Currently, clinical practice still offers standard RT protocols for patients with cancer affecting the same organ, without considering the molecular profile and the tumoral histotype, which may affect the RT outcome. Unfortunately, RT does not always lead to therapeutic benefits, due to distant metastatic spread and local recurrence, which induce radioresistance. Indeed, tumor radiosensitivity depends on many factors, some of which are linked to the clinical state and genetic background of the patient. The balance between radiosensitivity and radioresistance is regulated by different complex factors, including: the tumor stem cells, responsible for cancer repopulation within the RT schedule timespan; tumor-associated microenvironment features, such as hypoxia and the tumor–stroma interaction; an intrinsic and cell-dependent sensitivity to radiation; the modulation of DNA repair or other cell survival pathways in cancer.

In this scenario, the pivotal role of research in the field of radiobiology is to help clinicians in understanding the molecular portrait of a specific cancer type, in order to propose successful combinatorial anticancer therapies in clinical practice. Therefore, in the era of personalized medicine, prognostic and therapy-predictive molecular biomarkers are required to guide cancer therapeutic decisions between different RT modalities and schedules.

Thanks to high-throughput omics approaches such as proteogenomics, metabolomics, epigenomics, and radiomics, new instruments are now available for the diagnosis, to monitor the disease progression, and to predict radiosensitivity in many cancer types.

This Special Issue aims to provide new insights into the role of RT in different types of cancer in order to develop personalized therapies, and it will also highlight the use of combined approaches with new targeted agents. Other topics of interest to this Special Issue will be the discovery and analysis of radioresponse biomarkers reported by different in vitro, in vivo, or clinical studies.

Dr. Luigi Minafra
Dr. Francesco Paolo Cammarata
Dr. Marco Calvaruso
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 papers will be 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 2000 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

  • Radiotherapy 
  • Ionizing radiation 
  • Radiobiology 
  • Biomarkers 
  • Radioresistance 
  • Radiosensitivity 
  • Personalized treatments 
  • Theranostics 
  • “Omics” sciences

Published Papers (4 papers)

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Research

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Article
Targeted Next-Generation Sequencing for the Identification of Genetic Predictors of Radiation-Induced Late Skin Toxicity in Breast Cancer Patients: A Preliminary Study
J. Pers. Med. 2021, 11(10), 967; https://doi.org/10.3390/jpm11100967 - 27 Sep 2021
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Abstract
Normal tissue radiosensitivity is thought to be influenced by an individual’s genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we [...] Read more.
Normal tissue radiosensitivity is thought to be influenced by an individual’s genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2–3 subcutaneous fibrosis and/or grade 2–3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82–2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51–14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06–3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence. Full article
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Article
Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line
J. Pers. Med. 2021, 11(4), 308; https://doi.org/10.3390/jpm11040308 - 16 Apr 2021
Cited by 1 | Viewed by 750
Abstract
In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network [...] Read more.
In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT. Full article
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Article
Impact of Breast Size on Dosimetric Indices in Proton Versus X-ray Radiotherapy for Breast Cancer
J. Pers. Med. 2021, 11(4), 282; https://doi.org/10.3390/jpm11040282 - 08 Apr 2021
Cited by 1 | Viewed by 846
Abstract
Deep inspiration breath hold (DIBH) radiotherapy is a technique used to manage early stage left-sided breast cancer. This study compared dosimetric indices of patient-specific X-ray versus proton therapy DIBH plans to explore differences in target coverage, radiation doses to organs at risk, and [...] Read more.
Deep inspiration breath hold (DIBH) radiotherapy is a technique used to manage early stage left-sided breast cancer. This study compared dosimetric indices of patient-specific X-ray versus proton therapy DIBH plans to explore differences in target coverage, radiation doses to organs at risk, and the impact of breast size. Radiotherapy plans of sixteen breast cancer patients previously treated with DIBH radiotherapy were re-planned with hybrid inverse-planned intensity modulated X-ray radiotherapy (h-IMRT) and intensity modulated proton therapy (IMPT). The total prescribed dose was 40.05 Gy in 15 fractions for all cases. Comparisons between the clinical, h-IMRT, and IMPT evaluated doses to target volumes, organs at risk, and correlations between doses and breast size. Although no differences were observed in target volume coverage between techniques, the h-IMRT and IMPT were able to produce more even dose distributions and IMPT delivered significantly less dose to all organs at risk than both X-ray techniques. A moderate negative correlation was observed between breast size and dose to the target in X-ray techniques, but not IMPT. Both h-IMRT and IMPT produced plans with more homogeneous dose distribution than forward-planned IMRT and IMPT achieved significantly lower doses to organs at risk compared to X-ray techniques. Full article
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Review

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Review
Future Perspectives of Proton Therapy in Minimizing the Toxicity of Breast Cancer Radiotherapy
J. Pers. Med. 2021, 11(5), 410; https://doi.org/10.3390/jpm11050410 - 13 May 2021
Cited by 1 | Viewed by 1093
Abstract
The toxicity of radiotherapy is a key issue when analyzing the eligibility criteria for patients with breast cancer. In order to obtain better results, proton therapy is proposed because of the more favorable distribution of the dose in the patient’s body compared with [...] Read more.
The toxicity of radiotherapy is a key issue when analyzing the eligibility criteria for patients with breast cancer. In order to obtain better results, proton therapy is proposed because of the more favorable distribution of the dose in the patient’s body compared with photon radiotherapy. Scientific groups have conducted extensive research into the improved efficacy and lower toxicity of proton therapy for breast cancer. Unfortunately, there is no complete insight into the potential reasons and prospects for avoiding undesirable results. Cardiotoxicity is considered challenging; however, researchers have not presented any realistic prospects for preventing them. We compared the clinical evidence collected over the last 20 years, providing the rationale for the consideration of proton therapy as an effective solution to reduce cardiotoxicity. We analyzed the parameters of the dose distribution (mean dose, Dmax, V5, and V20) in organs at risk, such as the heart, blood vessels, and lungs, using the following two irradiation techniques: whole breast irradiation and accelerated partial breast irradiation. Moreover, we presented the possible causes of side effects, taking into account biological and technical issues. Finally, we collected potential improvements in higher quality predictions of toxic cardiac effects, like biomarkers, and model-based approaches to give the full background of this complex issue. Full article
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