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Molecular Pathology and Novel Therapies for Head and Neck Cancer

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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 (15 April 2024) | Viewed by 4208

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Special Issue Editor

Dr. Sabrina Wurzba

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Guest Editor

Faculty of Medicine, McGill University, Montreal, QC H3T 1E2, Canada
Interests: head and neck cancer; tumor progression; metastasis; molecular biology; genomics; epigenomics; translational medicine; personalized treatment; target and drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The number of new cases of head and neck cancer has noticeably rapidly increased in recent decades, especially among young adults. This is not only associated with tobacco and alcohol consumption, but due to HPV infection emerging as an additional risk factor, defining a new subtype of tumor that is distinct from “conventional” HPV‐negative ones. Head and neck cancer is remarkably heterogeneous, comprising several subtypes in different anatomic sites of the upper aerodigestive tracts (the nasal cavity, oral cavity, oropharynx, pharynx, hypopharynx, and larynx) with complex pathological and molecular features. Despite the advances in medical imaging and therapeutic approaches, the outcome of patients with advanced head and neck cancer remains poor, and the 5‐year survival is stagnant at <50%, with the lack of flexibility in therapeutic strategies often leading to patients suffering from inadequate or excessive treatments with severe side effects and lifelong consequences.

This Special Issue aims to expand the current molecular knowledge on treatment options and innovative approaches, one of the top priorities in the head and neck cancer field being to revert the obscure scenario of poor outcomes and improve patient survival. For this Special Issue, we welcome experts to contribute with review articles, clinical trial design and results, epidemiological data, bioinformatics and basic science information that can stimulate the critical discussion of the molecular pathology and novel therapies for head and neck cancers.

Any in silico data or pure clinical results will need to be supported with experimental data and will not be considered for review on its own.

Dr. Sabrina Wurzba
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

treatment options
therapeutic strategy
target therapy
personalized treatment
immunotherapy
chemotherapy
radiation therapy

Published Papers (3 papers)

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Research

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13 pages, 2561 KiB

Open AccessArticle

The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment

by César Rodríguez-Santana, Alba López-Rodríguez, Laura Martinez-Ruiz, Javier Florido, Olga Cela, Nazzareno Capitanio, Yolanda Ramírez-Casas, Darío Acuña-Castroviejo and Germaine Escames

Int. J. Mol. Sci. 2023, 24(19), 15030; https://doi.org/10.3390/ijms241915030 - 09 Oct 2023

Cited by 1 | Viewed by 1212

Abstract

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, which generates rhythmic changes in many physiological processes, including mitochondrial activity. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases such as cancer. Melatonin, whose production and secretion oscillates according to the light–dark cycle, is the principal regulator of clock gene expression. In addition, the oncostatic effects of melatonin correlate with an increase in mitochondrial activity. However, the direct links between circadian clock gene expression, mitochondrial activity, and the antiproliferative effects of melatonin in cancers, including head and neck squamous cell carcinoma (HNSCC), remain largely unknown. In this study, we analyzed the effects of melatonin on HNSCC cell lines (Cal-27 and SCC9), which were treated with 500 and 1000 µM melatonin. We found that the antiproliferative effect of melatonin is not mediated by the Bmal1 clock gene. Additionally, high doses of melatonin were observed to result in resynchronization of oscillatory circadian rhythm genes (Per2 and Sirt1). Surprisingly, the resynchronizing effect of melatonin on Per2 and Sirt1 did not produce alterations in the oscillation of mitochondrial respiratory activity. These results increase our understanding of the possible antiproliferative mechanisms in melatonin in the treatment of head and neck squamous cell carcinoma and suggest that its antiproliferative effects are independent of clock genes but are directly related to mitochondrial activity. Full article

(This article belongs to the Special Issue Molecular Pathology and Novel Therapies for Head and Neck Cancer)

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19 pages, 3036 KiB

Open AccessArticle

Establishment of a Machine Learning Model for the Risk Assessment of Perineural Invasion in Head and Neck Squamous Cell Carcinoma

by Christopher Weusthof, Sebastian Burkart, Karl Semmelmayer, Fabian Stögbauer, Bohai Feng, Karam Khorani, Sebastian Bode, Peter Plinkert, Karim Plath and Jochen Hess

Int. J. Mol. Sci. 2023, 24(10), 8938; https://doi.org/10.3390/ijms24108938 - 18 May 2023

Cited by 1 | Viewed by 2064

Abstract

Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion. Full article

(This article belongs to the Special Issue Molecular Pathology and Novel Therapies for Head and Neck Cancer)

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Review

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16 pages, 1966 KiB

Open AccessReview

Therapeutic Advances and Challenges for the Management of HPV-Associated Oropharyngeal Cancer

by Isis de Araújo Ferreira Muniz, Megan Araujo, Jenna Bouassaly, Fatemeh Farshadi, Mai Atique, Khashayar Esfahani, Paulo Rogerio Ferreti Bonan, Michael Hier, Marco Mascarella, Alex Mlynarek, Moulay Alaoui-Jamali and Sabrina Daniela da Silva

Int. J. Mol. Sci. 2024, 25(7), 4009; https://doi.org/10.3390/ijms25074009 - 03 Apr 2024

Viewed by 640

Abstract

The use of conventional chemotherapy in conjunction with targeted and immunotherapy drugs has emerged as an option to limit the severity of side effects in patients diagnosed with head and neck cancer (HNC), particularly oropharyngeal cancer (OPC). OPC prevalence has increased exponentially in the past 30 years due to the prevalence of human papillomavirus (HPV) infection. This study reports a comprehensive review of clinical trials registered in public databases and reported in the literature (PubMed/Medline, Scopus, and ISI web of science databases). Of the 55 clinical trials identified, the majority (83.3%) were conducted after 2015, of which 77.7% were performed in the United States alone. Eight drugs have been approved by the FDA for HNC, including both generic and commercial forms: bleomycin sulfate, cetuximab (Erbitux), docetaxel (Taxotere), hydroxyurea (Hydrea), pembrolizumab (Keytruda), loqtorzi (Toripalimab-tpzi), methotrexate sodium (Trexall), and nivolumab (Opdivo). The most common drugs to treat HPV-associated OPC under these clinical trials and implemented as well for HPV-negative HNC include cisplatin, nivolumab, cetuximab, paclitaxel, pembrolizumab, 5-fluorouracil, and docetaxel. Few studies have highlighted the necessity for new drugs specifically tailored to patients with HPV-associated OPC, where molecular mechanisms and clinical prognosis are distinct from HPV-negative tumors. In this context, we identified most mutated genes found in HPV-associated OPC that can represent potential targets for drug development. These include TP53, PIK3CA, PTEN, NOTCH1, RB1, FAT1, FBXW7, HRAS, KRAS, and CDKN2A. Full article

(This article belongs to the Special Issue Molecular Pathology and Novel Therapies for Head and Neck Cancer)

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