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Cancers
Special Issues
Combating Tumor Radioresistance
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Combating Tumor Radioresistance

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 9678

Special Issue Editors

Prof. Dr. Dirk Vordermark

E-Mail Website
Guest Editor
Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
Interests: radiation oncology; radiotherapy; radiobiology; tumor microenvironment; tumor oxygenation;
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. María Isabel Núñez

E-Mail Website
Guest Editor
Department of Radiology and Physical Medicine, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research University of Granada, 18016 Granada, Spain
Interests: radiation resistance; tumor microenvironment; breast cancer; tumor biomarkers; radiobiology;

Special Issue Information

Dear Colleagues,

Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% of all cancer patients either alone or in combination with other treatments. Despite the technological advances in RT, which allow a more precise delivery of radiation while progressively minimizing the impact on normal tissues, radioresistance and tumor recurrence remain important challenges. Tumor heterogeneity is responsible for the variation in the radiation response of the different tumor subpopulations. A main factor related to radioresistance is the presence of cancer stem cells (CSC) inside tumors, which are responsible for metastases, relapses, RT failure, and a poor prognosis in cancer patients.

No theory can yet explain the association between the physical characteristics of high LET radiation or high radiation dose and their biological effects RT causes cancer cell death; nevertheless, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metabolic alterations in cancer cells are closely associated with the EMT and CSC phenotypes. IR can also elicit various changes in the tumour microenvironment (TME) that may affect invasion and metastasis. RT induces immunogenic cell death also contributing to tumor control through the abscopal effect. More research is also needed regarding the great potential of particle therapy in radioresistant cancers. Moreover, the identification of targetable pathways in combination with radiation is also of great interest in this issue. This information would be essential to understand tumor radioresistance and to improve patient care.

This special issue will include reports of pre-clinical data on all aspects modulating radioresistance of tumor cells in experimental systems in vitro and in vivo, including combinations of ionizing radiation with novel substances, e. g. immunotherapy, targeted therapy or chemotherapy. In addition, reports on prospective and retrospective clinical trials and case series focusing on tumor control and tumor radioresistance will be central to the special issue. Clinical contributions will include all advanced methods of photon and particle radiotherapy.

Prof. Dr. Dirk Vordermark
Prof. Dr. María Isabel Núñez
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 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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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
  • radioresistance
  • radiosensitivity
  • tumor control
  • tumor microenvironment
  • immunotherapy
  • cell death

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Published Papers (4 papers)

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Research

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14 pages, 3647 KiB  
Article
The Microbeam Insert at the White Beam Beamline P61A at the Synchrotron PETRA III/DESY: A New Tool for High Dose Rate Irradiation Research
by Elisabeth Schültke, Stefan Fiedler, Catharina Mewes, Elisabetta Gargioni, Johannes Klingenberg, Guilherme Abreu Faria, Michael Lerch, Marco Petasecca, Franziska Prehn, Marie Wegner, Marten Scholz, Felix Jaekel and Guido Hildebrandt
Cancers 2022, 14(20), 5137; https://doi.org/10.3390/cancers14205137 - 20 Oct 2022
Cited by 2 | Viewed by 1942
Abstract
High dose rate radiotherapies such as FLASH and microbeam radiotherapy (MRT) both have developed to the stage of first veterinary studies within the last decade. With the development of a new research tool for high dose rate radiotherapy at the end station P61A [...] Read more.
High dose rate radiotherapies such as FLASH and microbeam radiotherapy (MRT) both have developed to the stage of first veterinary studies within the last decade. With the development of a new research tool for high dose rate radiotherapy at the end station P61A of the synchrotron beamline P61 on the DESY campus in Hamburg, we increased the research capacity in this field to speed up the translation of the radiotherapy techniques which are still experimental, from bench to bedside. At P61, dose rates of several hundred Gy/s can be delivered. Compared to dedicated biomedical beamlines, the beam width available for MRT experiments is a very restrictive factor. We developed two model systems specifically to suit these specific technical parameters and tested them in a first set of experiments. Full article
(This article belongs to the Special Issue Combating Tumor Radioresistance)
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Review

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16 pages, 1044 KiB  
Review
P38 MAPK and Radiotherapy: Foes or Friends?
by Natalia García-Flores, Jaime Jiménez-Suárez, Cristina Garnés-García, Diego M. Fernández-Aroca, Sebastia Sabater, Ignacio Andrés, Antonio Fernández-Aramburo, María José Ruiz-Hidalgo, Borja Belandia, Ricardo Sanchez-Prieto and Francisco J. Cimas
Cancers 2023, 15(3), 861; https://doi.org/10.3390/cancers15030861 - 30 Jan 2023
Cited by 4 | Viewed by 2294
Abstract
Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in [...] Read more.
Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in key processes triggered by IR-mediated genotoxic insult, such as the cell cycle, apoptosis or senescence. However, we do not yet have a definitive clue about the role of p38 MAPK in terms of radioresistance/sensitivity and its potential use to improve current radiotherapy. In this review, we summarize the current knowledge on this family of MAPKs in response to IR as well as in different aspects related to radiotherapy, such as their role in the control of REDOX, fibrosis, and in the radiosensitizing effect of several compounds. Full article
(This article belongs to the Special Issue Combating Tumor Radioresistance)
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26 pages, 1544 KiB  
Review
Radiotherapeutic Strategies to Overcome Resistance of Breast Cancer Brain Metastases by Considering Immunogenic Aspects of Cancer Stem Cells
by Katharina Hintelmann, Cordula Petersen and Kerstin Borgmann
Cancers 2023, 15(1), 211; https://doi.org/10.3390/cancers15010211 - 29 Dec 2022
Cited by 3 | Viewed by 2071
Abstract
Breast cancer is the most diagnosed cancer in women, and symptomatic brain metastases (BCBMs) occur in 15–20% of metastatic breast cancer cases. Despite technological advances in radiation therapy (RT), the prognosis of patients is limited. This has been attributed to radioresistant breast cancer [...] Read more.
Breast cancer is the most diagnosed cancer in women, and symptomatic brain metastases (BCBMs) occur in 15–20% of metastatic breast cancer cases. Despite technological advances in radiation therapy (RT), the prognosis of patients is limited. This has been attributed to radioresistant breast cancer stem cells (BCSCs), among other factors. The aim of this review article is to summarize the evidence of cancer-stem-cell-mediated radioresistance in brain metastases of breast cancer from radiobiologic and radiation oncologic perspectives to allow for the better interpretability of preclinical and clinical evidence and to facilitate its translation into new therapeutic strategies. To this end, the etiology of brain metastasis in breast cancer, its radiotherapeutic treatment options, resistance mechanisms in BCSCs, and effects of molecularly targeted therapies in combination with radiotherapy involving immune checkpoint inhibitors are described and classified. This is considered in the context of the central nervous system (CNS) as a particular metastatic niche involving the blood–brain barrier and the CNS immune system. The compilation of this existing knowledge serves to identify possible synergistic effects between systemic molecularly targeted therapies and ionizing radiation (IR) by considering both BCSCs’ relevant resistance mechanisms and effects on normal tissue of the CNS. Full article
(This article belongs to the Special Issue Combating Tumor Radioresistance)
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20 pages, 739 KiB  
Review
Molecular Radiobiology in Non-Small Cell Lung Cancer: Prognostic and Predictive Response Factors
by Javier Peinado-Serrano and Amancio Carnero
Cancers 2022, 14(9), 2202; https://doi.org/10.3390/cancers14092202 - 28 Apr 2022
Cited by 4 | Viewed by 2589
Abstract
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, generating huge economic and social impacts that have not slowed in recent years. Oncological treatment for this neoplasm usually includes surgery, chemotherapy, treatments on molecular targets and ionizing radiation. The prognosis [...] Read more.
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, generating huge economic and social impacts that have not slowed in recent years. Oncological treatment for this neoplasm usually includes surgery, chemotherapy, treatments on molecular targets and ionizing radiation. The prognosis in terms of overall survival (OS) and the different therapeutic responses between patients can be explained, to a large extent, by the existence of widely heterogeneous molecular profiles. The identification of prognostic and predictive gene signatures of response to cancer treatment, could help in making therapeutic decisions in patients affected by NSCLC. Given the published scientific evidence, we believe that the search for prognostic and/or predictive gene signatures of response to radiotherapy treatment can significantly help clinical decision-making. These signatures may condition the fractions, the total dose to be administered and/or the combination of systemic treatments in conjunction with radiation. The ultimate goal is to achieve better clinical results, minimizing the adverse effects associated with current cancer therapies. Full article
(This article belongs to the Special Issue Combating Tumor Radioresistance)
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