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Counteracting Radioresistance Using the Optimization of Radiotherapy
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Counteracting Radioresistance Using the Optimization of Radiotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 19561

Special Issue Editor

Dr. François Chevalier

E-Mail Website
Guest Editor
UMR6252 CIMAP-Centre de Recherche sur les Ions, les MAtériaux et la Photonique Team ARIA, Applications in Radiobiology with Accelerated Ions Campus Jules, Horowitz, Bd Henri Becquerel, BP 55027, Cedex 05, F-14076 Caen, France
Interests: cancer cell biology; radiotherapy; particle therapy; DNA damage response; signaling transduction; radiation-induced bystander effects; tumor cell radio-sensitization, integrated omics; proteomics; radiation response biomarkers; radioresistance; combined treatments; tumor microenvironment; inflammatory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor radioresistance is associated with a failure to achieve loco-regional disease control following radiotherapy with the highest acceptable doses. Radiobiology research focused on tumor radioresistance has pointed out several mechanisms attenuating the efficacy of tumor irradiation and several treatment answers to overcome such radio-resistance. Personalized medecine allows us to adapt the treatment to diseases according to patient specificities and characteristics. For examples, genetic mutations on DNA repair genes open the possibility of synthetic lethality using targeted inhibitors, and hypoxia in the tumoral micro-environment can be weakened with localized chemotherapy associated with accurate imaging. Novel radiotherapy such as heavy ion therapy enable a better balance between high doses to the tumor and low doses to the surrounding healthy tissues. The combined treatment of radiotherapy with specialized chemotherapy and immunotherapy are under developement to reduce radioresistance, secondary cancer recovery and metastases emergence.

I am pleased to invite you to participate to this Special Issue "Counteracting Radioresistance Using the Optimization of Radiotherapy". Research papers, up-to-date review articles, and commentaries are all welcome.

Dr. François Chevalier
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Hadrontherapy
  • DNA damages repair
  • Combined treatments
  • Micro-environment
  • Stem cells
  • Hypoxia
  • Protons
  • Carbon ions

Published Papers (6 papers)

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Editorial

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2 pages, 163 KiB  
Editorial
Counteracting Radio-Resistance Using the Optimization of Radiotherapy
by François Chevalier
Int. J. Mol. Sci. 2020, 21(5), 1767; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051767 - 05 Mar 2020
Cited by 5 | Viewed by 1709
Abstract
Radiotherapy is an essential component of cancer therapy and remains one of the most (cost-) effective treatment options available [...] Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)

Research

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16 pages, 14809 KiB  
Article
TiO2 Nanomaterials Non-Controlled Contamination Could Be Hazardous for Normal Cells Located in the Field of Radiotherapy
by Yidan Wang, Allan Sauvat, Celine Lacrouts, Jérôme Lebeau, Romain Grall, Marie Hullo, Fabrice Nesslany and Sylvie Chevillard
Int. J. Mol. Sci. 2020, 21(3), 940; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030940 - 31 Jan 2020
Cited by 3 | Viewed by 2133
Abstract
Among nanomaterials (NMs), titanium dioxide (TiO2) is one of the most manufactured NMs and can be found in many consumers’ products such as skin care products, textiles and food (as E171 additive). Moreover, due to its most attractive property, a photoactivation [...] Read more.
Among nanomaterials (NMs), titanium dioxide (TiO2) is one of the most manufactured NMs and can be found in many consumers’ products such as skin care products, textiles and food (as E171 additive). Moreover, due to its most attractive property, a photoactivation upon non-ionizing UVA radiation, TiO2 NMs is widely used as a decontaminating agent. Uncontrolled contaminations by TiO2 NMs during their production (professional exposure) or by using products (consumer exposure) are rather frequent. So far, TiO2 NMs cytotoxicity is still a matter of controversy depending on biological models, types of TiO2 NMs, suspension preparation and biological endpoints. TiO2 NMs photoactivation has been widely described for UV light radiation exposure, it could lead to reactive oxygen species production, known to be both cyto- and genotoxic on human cells. After higher photon energy exposition, such as X-rays used for radiotherapy and for medical imaging, TiO2 NMs photoactivation still occurs. Importantly, the question of its hazard in the case of body contamination of persons receiving radiotherapy was never addressed, knowing that healthy tissues surrounding the tumor are indeed exposed. The present work focuses on the analysis of human normal bronchiolar cell response after co-exposition TiO2 NMs (with different coatings) and ionizing radiation. Our results show a clear synergistic effect, in terms of cell viability, cell death and oxidative stress, between TiO2 NMS and radiation. Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)
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9 pages, 2257 KiB  
Communication
FGFR Signaling as a Candidate Therapeutic Target for Cancers Resistant to Carbon Ion Radiotherapy
by Narisa Dewi Maulany Darwis, Ankita Nachankar, Yasushi Sasaki, Toshiaki Matsui, Shin-ei Noda, Kazutoshi Murata, Tomoaki Tamaki, Ken Ando, Noriyuki Okonogi, Shintaro Shiba, Daisuke Irie, Takuya Kaminuma, Takuya Kumazawa, Mai Anakura, Souichi Yamashita, Takashi Hirakawa, Sangeeta Kakoti, Yuka Hirota, Takashi Tokino, Akira Iwase, Tatsuya Ohno, Atsushi Shibata, Takahiro Oike and Takashi Nakanoadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2019, 20(18), 4563; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184563 - 14 Sep 2019
Cited by 12 | Viewed by 2971
Abstract
Radiotherapy is an essential component of cancer therapy. Carbon ion radiotherapy (CIRT) promises to improve outcomes compared with standard of care in many cancers. Nevertheless, clinicians often observe in-field recurrence after CIRT. This indicates the presence of a subset of cancers that harbor [...] Read more.
Radiotherapy is an essential component of cancer therapy. Carbon ion radiotherapy (CIRT) promises to improve outcomes compared with standard of care in many cancers. Nevertheless, clinicians often observe in-field recurrence after CIRT. This indicates the presence of a subset of cancers that harbor intrinsic resistance to CIRT. Thus, the development of methods to identify and sensitize CIRT-resistant cancers is needed. To address this issue, we analyzed a unique donor-matched pair of clinical specimens: a treatment-naïve tumor, and the tumor that recurred locally after CIRT in the same patient. Exon sequencing of 409 cancer-related genes identified enrichment of somatic mutations in FGFR3 and FGFR4 in the recurrent tumor compared with the treatment-naïve tumor, indicating a pivotal role for FGFR signaling in cancer cell survival through CIRT. Inhibition of FGFR using the clinically available pan-FGFR inhibitor LY2874455 sensitized multiple cancer cell lines to carbon ions at 3 Gy (RBE: relative biological effectiveness), the daily dose prescribed to the patient. The sensitizer enhancement ratio was 1.66 ± 0.17, 1.27 ± 0.09, and 1.20 ± 0.18 in A549, H1299, and H1703 cells, respectively. Our data indicate the potential usefulness of the analytical pipeline employed in this pilot study to identify targetable mutations associated with resistance to CIRT, and of LY21874455 as a sensitizer for CIRT-resistant cancers. The results warrant validation in larger cohorts. Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)
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10 pages, 2405 KiB  
Communication
Radiosensitivity Differences between EGFR Mutant and Wild-Type Lung Cancer Cells are Larger at Lower Doses
by Mai Anakura, Ankita Nachankar, Daijiro Kobayashi, Napapat Amornwichet, Yuka Hirota, Atsushi Shibata, Takahiro Oike and Takashi Nakano
Int. J. Mol. Sci. 2019, 20(15), 3635; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20153635 - 25 Jul 2019
Cited by 17 | Viewed by 3405
Abstract
In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. [...] Read more.
In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and β were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann–Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/β were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation. Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)
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Review

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22 pages, 693 KiB  
Review
Hadrontherapy Interactions in Molecular and Cellular Biology
by Juliette Thariat, Samuel Valable, Carine Laurent, Siamak Haghdoost, Elodie A. Pérès, Myriam Bernaudin, François Sichel, Paul Lesueur, Mathieu Césaire, Edwige Petit, Aurélie E. Ferré, Yannick Saintigny, Sven Skog, Mihaela Tudor, Michael Gérard, Sebastien Thureau, Jean-Louis Habrand, Jacques Balosso and François Chevalier
Int. J. Mol. Sci. 2020, 21(1), 133; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010133 - 24 Dec 2019
Cited by 16 | Viewed by 4536
Abstract
The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to [...] Read more.
The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers. Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)
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Other

10 pages, 3228 KiB  
Technical Note
Robustness of Clonogenic Assays as a Biomarker for Cancer Cell Radiosensitivity
by Toshiaki Matsui, Endang Nuryadi, Shuichiro Komatsu, Yuka Hirota, Atsushi Shibata, Takahiro Oike and Takashi Nakano
Int. J. Mol. Sci. 2019, 20(17), 4148; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20174148 - 25 Aug 2019
Cited by 34 | Viewed by 4272
Abstract
Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications [...] Read more.
Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF2 (surviving fraction after 2 Gy irradiation) and for D10 (dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF2 and D10 have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF2 and D10 as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons. Full article
(This article belongs to the Special Issue Counteracting Radioresistance Using the Optimization of Radiotherapy)
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