Special Issue "Tumor Radioresistance"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 30 April 2019

Special Issue Editors

Guest Editor
Prof. Dr. Jan Bussink

Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
Website | E-Mail
Interests: Radioresistance; tumor microenvironment; tumor cell hypoxia; EGFR signaling; tumor cell metabolism; tumor vasculature; non-invasive PET imaging; lung cancer
Guest Editor
Dr. Paul Span

Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
Website | E-Mail
Interests: tumor microenviroment; breast cancer; head and neck cancer; radiotherapy; hypoxia; biobanking

Special Issue Information

Dear Colleagues,

Radiotherapy is given to a majority of patients with cancer, and remains one of the most (cost)effective treatment options available. However, several mechanisms attenuating the efficacy of tumor irradiation have long been known to occur, such as hypoxia, DNA damage repair, repopulation and cell cycle redistribution. Radiobiology research into tumor radioresistance has thus focused on targeting these mechanisms to increase radiotherapy effectiveness by e.g. hypoxia modification, or using combination therapy with DNA damage repair or growth factor receptor inhibitors and reducing the overall treatment time.

The impact of some of these classic mechanisms on tumor radioresistance has changed, however, with the widespread use of novel radiotherapy regimens such as heavy ions/particles, stereotactic radiotherapy, radiotherapy and immunotherapy combination, etc.. Additionally, recent insights in additional mechanisms such as stem cells/stemness, tumor metabolism, and effect of irradiation on the immune system has lead to rapid development of additional targets for combination therapy with irradiation.

We aim to describe these new aspects identifying and overcoming tumor radioresistance in this Special Issue of Cancers, and welcome all contributions to this field.

Prof. Dr. Jan Bussink
Dr. Paul Span
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. Cancers 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 1800 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

  • Hypoxia
  • DNA damage repair
  • Metabolism
  • Radiotherapy-immunotherapy combinations
  • Protons
  • Stem cells
  • Tumor cell proliferation

Published Papers (3 papers)

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Research

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Open AccessArticle Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation
Cancers 2019, 11(2), 127; https://doi.org/10.3390/cancers11020127
Received: 23 November 2018 / Revised: 4 January 2019 / Accepted: 15 January 2019 / Published: 22 January 2019
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Abstract
Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% [...] Read more.
Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy. Full article
(This article belongs to the Special Issue Tumor Radioresistance)
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Open AccessArticle The Response of Prostate Cancer to Androgen Deprivation and Irradiation Due to Immune Modulation
Received: 1 December 2018 / Revised: 18 December 2018 / Accepted: 21 December 2018 / Published: 26 December 2018
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Abstract
This study investigated changes in the immune system and the biological consequences of androgen deprivation therapy (ADT) and radiotherapy (RT) for augmenting the treatment response in prostate cancer, particularly for castration-resistant prostate cancer (CRPC). Human and murine prostate cancer cell lines were used [...] Read more.
This study investigated changes in the immune system and the biological consequences of androgen deprivation therapy (ADT) and radiotherapy (RT) for augmenting the treatment response in prostate cancer, particularly for castration-resistant prostate cancer (CRPC). Human and murine prostate cancer cell lines were used to examine the response to ADT and RT in vitro and in vivo. Biological changes following treatment and related immune modulation in the tumor microenvironment were examined. Our results showed that CRPC cells were demonstrated to be more resistant to the RT and ADT treatments. ADT increased tumor inhibition following irradiation. The underlying changes included increased cell death, attenuated myeloid-derived suppressor cell recruitment, and an increase in the number of tumor-infiltrating T cells (TILs). Furthermore, when high-dose fractionated RT was given to the primary CRPC tumor, a smaller size of secondary non-irradiated tumor associated with increased TILs was noted in ADT-treated mice. In conclusion, treatment resistance in CRPC was associated with a more immunosuppressive microenvironment. Enhanced antitumor immunity was responsible for the augmented RT-induced tumoricidal effect induced by ADT. Immune modulation could be a promising strategy for prostate cancer, especially for metastatic CRPC. Full article
(This article belongs to the Special Issue Tumor Radioresistance)
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Review

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Open AccessReview Extracellular Vesicles as Transmitters of Hypoxia Tolerance in Solid Cancers
Cancers 2019, 11(2), 154; https://doi.org/10.3390/cancers11020154
Received: 20 December 2018 / Revised: 23 January 2019 / Accepted: 24 January 2019 / Published: 29 January 2019
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Abstract
Tumour hypoxia is a common feature of solid tumours that contributes to poor prognosis after treatment. This is mainly due to increased resistance of hypoxic cells to radio- and chemotherapy and the association of hypoxic cells with increased metastasis development. It is therefore [...] Read more.
Tumour hypoxia is a common feature of solid tumours that contributes to poor prognosis after treatment. This is mainly due to increased resistance of hypoxic cells to radio- and chemotherapy and the association of hypoxic cells with increased metastasis development. It is therefore not surprising that an increased hypoxic tumour fraction is associated with poor patient survival. The extent of hypoxia within a tumour is influenced by the tolerance of individual tumor cells to hypoxia, a feature that differs considerably between tumors. High numbers of hypoxic cells may, therefore, be a direct consequence of enhanced cellular capability inactivation of hypoxia tolerance mechanisms. These include HIF-1α signaling, the unfolded protein response (UPR) and autophagy to prevent hypoxia-induced cell death. Recent evidence shows hypoxia tolerance can be modulated by distant cells that have experienced episodes of hypoxia and is mediated by the systemic release of factors, such as extracellular vesicles (EV). In this review, the evidence for transfer of a hypoxia tolerance phenotype between tumour cells via EV is discussed. In particular, proteins, mRNA and microRNA enriched in EV, derived from hypoxic cells, that impact HIF-1α-, UPR-, angiogenesis- and autophagy signalling cascades are listed. Full article
(This article belongs to the Special Issue Tumor Radioresistance)
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