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Cancers
Special Issues
Emerging Biomarkers Used in Radiochemotherapy
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Emerging Biomarkers Used in Radiochemotherapy

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 11472

Special Issue Editors

Dr. Markus Schirmer

E-Mail Website
Guest Editor
Department of Radiotherapy and Radiation Oncology, University Medicine Goettingen (UMG), Robert-Koch-Str. 40, 37075 Goettingen, Germany
Interests: radiochemotherapy; biomarkers; genetics; germline polymorphisms; gastrointestinal cancer; urological cancer
Prof. Dr. Stefan Rieken

E-Mail Website
Guest Editor
Department of Radiotherapy and Radiation Oncology, University Medicine Goettingen (UMG), Robert-Koch-Str. 40, 37075 Goettingen, Germany
Interests: precision radiotherapy; radioimmunotherapy; lung cancer; HNSCC; CNS malignancies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Unlike great advances made in targeted chemotherapy by profiling tumors for addressable mutations, no such treatment individualization has been achieved yet for radiotherapy or combined radiochemotherapy. Given the broad spectra of both treatment outcomes and side-effects, a substantial impact of tumors and host biomarkers is presumed. With the rapid progress in the technical exploration of molecular features in the (epi-)genome, transcriptome, proteome, and metabolome there is an emerging potential for the discovery of promising biomarkers in radiochemotherapy. This Special Issue invites experts in this field to present and discuss data on prognostic and predictive biomarkers assessed in retrospective and prospective clinical cohorts with various kinds of radiotherapy or radiochemotherapy applied. Sophisticated data on functional mechanisms of biomarkers are also welcome.

Dr. Markus Schirmer
Prof. Dr. Stefan Rieken
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
  • radiochemotherapy
  • biomarkers
  • genetics
  • genomics
  • genome
  • epigenome
  • transcriptome
  • proteome
  • metabolome
  • tumor genome
  • host genome
  • single nucleotide polymorphisms
  • cytokines

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Published Papers (4 papers)

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13 pages, 1996 KiB  
Article
Targeting STAT3 Signaling Facilitates Responsiveness of Pancreatic Cancer Cells to Chemoradiotherapy
by Hannah Flebbe, Melanie Spitzner, Philipp Enno Marquet, Jochen Gaedcke, B. Michael Ghadimi, Stefan Rieken, Günter Schneider, Alexander O. Koenig and Marian Grade
Cancers 2022, 14(5), 1301; https://doi.org/10.3390/cancers14051301 - 3 Mar 2022
Cited by 6 | Viewed by 2398
Abstract
The debate is ongoing regarding the potential role of preoperative chemoradiotherapy (CRT) for patients with pancreatic ductal adenocarcinoma (PDAC), and whether it should be reserved for borderline resectable or unresectable tumors. However, treatment response is heterogeneous, implicating the need to unveil and overcome [...] Read more.
The debate is ongoing regarding the potential role of preoperative chemoradiotherapy (CRT) for patients with pancreatic ductal adenocarcinoma (PDAC), and whether it should be reserved for borderline resectable or unresectable tumors. However, treatment response is heterogeneous, implicating the need to unveil and overcome the underlying mechanisms of resistance. Activation of the transcription factor STAT3 was recently linked to CRT resistance in other gastrointestinal cancers such as rectal and esophageal cancers, but its role in PDAC needs to be clarified. Protein expression and phosphorylation of STAT3 was determined in PDAC cell lines and connected to transcriptional activity measured by dual-luciferase reporter gene assays. Inhibition of STAT3 signaling was achieved by RNAi or the small-molecule inhibitor napabucasin. We observed a positive correlation between STAT3 signaling activity and CRT resistance. Importantly, genetical and pharmacological perturbation of the IL-6/STAT3 pathway resulted in CRT sensitization specifically in those cell lines, in which STAT3 activity was augmented by IL-6. In conclusion, our data underscore the general importance of IL-6/STAT3 signaling for CRT resistance and suggest that pathway inhibition may represents a putative treatment strategy in order to increase the fraction of patients with PDAC who are candidates for surgical approaches. Full article
(This article belongs to the Special Issue Emerging Biomarkers Used in Radiochemotherapy)
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15 pages, 2999 KiB  
Article
Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1
by Manuel Guhlich, Laura Hubert, Caroline Patricia Nadine Mergler, Margret Rave-Fraenk, Leif Hendrik Dröge, Martin Leu, Heinz Schmidberger, Stefan Rieken, Andrea Hille and Markus Anton Schirmer
Cancers 2021, 13(21), 5585; https://doi.org/10.3390/cancers13215585 - 8 Nov 2021
Cited by 3 | Viewed by 2124
Abstract
Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with [...] Read more.
Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFβ1 ligand) and TGFBR1 (TGFβ receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41–3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified. Full article
(This article belongs to the Special Issue Emerging Biomarkers Used in Radiochemotherapy)
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19 pages, 2317 KiB  
Article
8-Oxoguanine DNA Glycosylase (OGG1) Cys326 Variant: Increased Risk for Worse Outcome of Patients with Locally Advanced Rectal Cancer after Multimodal Therapy
by Martin Leu, Theresa Riebeling, Leif Hendrik Dröge, Laura Hubert, Manuel Guhlich, Hendrik Andreas Wolff, Jürgen Brockmöller, Jochen Gaedcke, Stefan Rieken and Markus Anton Schirmer
Cancers 2021, 13(11), 2805; https://doi.org/10.3390/cancers13112805 - 4 Jun 2021
Cited by 2 | Viewed by 2364
Abstract
Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related [...] Read more.
Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer. Full article
(This article belongs to the Special Issue Emerging Biomarkers Used in Radiochemotherapy)
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16 pages, 719 KiB  
Systematic Review
Cognitive Decline following Radiotherapy of Head and Neck Cancer: Systematic Review and Meta-Analysis of MRI Correlates
by Noor Shatirah Voon, Hanani Abdul Manan and Noorazrul Yahya
Cancers 2021, 13(24), 6191; https://doi.org/10.3390/cancers13246191 - 8 Dec 2021
Cited by 23 | Viewed by 3639
Abstract
Radiotherapy for head and neck cancers exposes small parts of the brain to radiation, resulting in radiation-induced changes in cerebral tissue. In this review, we determine the correlation between cognitive deterioration in patients with head and neck cancer after radiotherapy and magnetic resonance [...] Read more.
Radiotherapy for head and neck cancers exposes small parts of the brain to radiation, resulting in radiation-induced changes in cerebral tissue. In this review, we determine the correlation between cognitive deterioration in patients with head and neck cancer after radiotherapy and magnetic resonance imaging (MRI) changes. Systematic searches were performed in PubMed, Scopus, and Cochrane databases in February 2021. Studies of head and neck cancer patients treated with radiotherapy and periodical cognitive and MRI assessments were included. Meta-analysis was performed to analyse the correlation of Montreal Cognitive Assessment (MoCA) scores to MRI structural and functional changes. Seven studies with a total of 404 subjects (irradiated head and neck patients, n = 344; healthy control, n = 60) were included. Most studies showed the significance of MRI in detecting microstructural and functional changes in association with neurocognitive function. The changes were seen in various brain areas, predominantly the temporal region, which also shows dose dependency (6/7 studies). An effect size (r = 0.43, p < 0.001) was reported on the correlation of MoCA scores to MRI structural and functional changes with significant correlations shown among patients treated with head and neck radiotherapy. However, the effect size appears modest. Full article
(This article belongs to the Special Issue Emerging Biomarkers Used in Radiochemotherapy)
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