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Cells
Special Issues
Head and Neck Cancer: From Mechanisms to Therapeutics
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Head and Neck Cancer: From Mechanisms to Therapeutics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1397

Special Issue Editors

Dr. Jozsef Dudas

E-Mail Website
Guest Editor
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria
Interests: epithelial-to-mesenchymal transition; fibroblasts; chemokines; head and neck squamous cell carcinoma; curcumin; tumor progression
Special Issues, Collections and Topics in MDPI journals
Dr. José Angelito U. Hardillo

E-Mail Website
Guest Editor
Department of Otorhinolaryngology Head and Neck Surgery, Erasmus MC, 3015 GD Rotterdam, The Netherlands
Interests: head and neck cancer; sinonasal/skullbase tumors; translational research; tumor recurrence and distant metastasis; tumor microenvironment; tumor heterogeneity
Special Issues, Collections and Topics in MDPI journals
Dr. Federica Ganci

E-Mail Website
Guest Editor
IRCCS Regina Elena National Cancer Institute, Roma, Italy
Interests: head and neck squamous cell carcinoma; long non-coding RNAs

Special Issue Information

Dear Colleagues,

Head and Neck Cancer (HNC) is responsible for over one million deaths worldwide (Bray et al. CA Cancer J. Clin. 2018, 68, 394–424.) The several localisations of HNC include the oral cavity, upper aerodigestive tract (including the pharynx, hypopharynx, and larynx), the sinuses, salivary glands, and the bone and soft tissue of the head and neck (Pezzuto et al. Oncology 2015, 89, 125–136.) The incidences of various localisations are different, for example, oropharynx carcinoma is most frequent in Europe, while nasopharynx carcinoma in Southeast Asia (International Agency for Research of Cancer). A slight improvement in the first therapy response up to 60% is achieved. In the background of HNC risk factors, the use of tobacco products, consumption of alcohol, genetics, age, and human papillomavirus (HPV) or Epstein‒Barr virus infections (Pezzuto et al., 2015) all cause potential immunological responses against HNC. A great challenge of HNC is its great heterogeneity: among patients, in single tumors and even within one cancer cell nest. This makes it difficult to identify and standardize drivers for targeted therapy. HNC also develops several forms of therapy resistance including multiple types of resistance against immunotherapy. Our aim is to provide a valuable Special Issue on novel approaches in HNC biomechanistic research and their clinical applications in order to improve the therapeutical expectations.

Dr. Jozsef Dudas
Dr. José Hardillo
Dr. Federica Ganci
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 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. Cells 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 2700 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

  • immunotherapy
  • immune checkpoint
  • driver mutations
  • predictive factors
  • spatial gene expression analysis
  • single cell sequencing
  • epithelial‒mesenchymal transdifferentiation

Published Papers (1 paper)

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Research

19 pages, 4181 KiB  
Article
Different Impacts of DNA-PK and mTOR Kinase Inhibitors in Combination with Ionizing Radiation on HNSCC and Normal Tissue Cells
by Nina Klieber, Laura S. Hildebrand, Eva Faulhaber, Julia Symank, Nicole Häck, Annamaria Härtl, Rainer Fietkau and Luitpold V. Distel
Cells 2024, 13(4), 304; https://doi.org/10.3390/cells13040304 - 06 Feb 2024
Viewed by 957
Abstract
Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used [...] Read more.
Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used simultaneously with ionizing radiation (IR) in cancer treatment. Our study focused on the selective DNA-PK-inhibitor AZD7648; the selective mTOR-inhibitor Sapanisertib; and CC-115, a dual inhibitor targeting both mTOR and DNA-PK. The impact of these KIs on HNSCC and normal tissue cells was assessed using various analytical methods including cell death studies, cell cycle analysis, real-time microscopy, colony-forming assays and immunohistochemical staining for γH2AX and downstream mTOR protein p-S6. We detected a strong inhibition of IR-induced DNA double-strand break (DSB) repair, particularly in AZD7648-treated HNSCC, whereas normal tissue cells repaired DNA DSB more efficiently. Additionally, AZD7648 + IR treatment showed a synergistic decline in cell proliferation and clonogenicity, along with an elevated G2/M arrest and cell death in the majority of HNSCC cell lines. CC-115 + IR treatment led to an elevation in G2/M arrest, increased cell death, and a synergistic reduction in cell proliferation, though the effect was notably lower compared to the AZD7648 + IR- treated group. Sapanisertib led to a high cellular toxicity in both HNSCC and normal tissue cells, even in non-irradiated cells. Regarding cell proliferation and the induction of apoptosis and necrosis, Sapanisertib + IR was beneficial only in HPV+ HNSCC. Overall, this study highlights the potential of AZD7648 as a radiosensitizing agent in advanced-stage HPV-positive and negative HNSCC, offering a promising therapeutic strategy. However, the dual mTOR/DNA-PK-I CC-115 did not provide a distinct advantage over the use of selective KIs in our investigations, suggesting limited benefits for its application in KI + IR therapy. Notably, the selective mTOR-inhibitor Sapanisertib was only beneficial in HPV+ HNSCC and should not be applied in HPV− cases. Full article
(This article belongs to the Special Issue Head and Neck Cancer: From Mechanisms to Therapeutics)
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