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Pathogenesis and Treatments of Head and Neck Cancer
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Pathogenesis and Treatments of Head and Neck Cancer

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: 20 October 2024 | Viewed by 5858

Special Issue Editor

Dr. Marko Tarle

E-Mail Website
Guest Editor
1. Department of Maxillofacial Surgery, Dubrava University Hospital, 10 000 Zagreb, Croatia
2. School of Dental Medicine, University of Zagreb, 10 000 Zagreb, Croatia
Interests: oral cancer; head and neck cancer; cancer therapy; molecular biomarkers; maxillofacial surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck cancer (HNSCC) is the sixth most common cancer worldwide and is a major public health problem due to its high mortality rate, despite the strong development of diagnostic and therapeutic methods in recent decades. The main risk factors are the consumption of alcohol and tobacco products and human papillomavirus (HPV) infection, which is responsible for a significant increase in incidence in the younger population. Patients with the same clinical and patho-histologic features often have a different disease prognosis. This suggests that the biological behavior of HNSCC and interpersonal differences require further investigation. New biomarkers that can help us diagnose tumors early, more accurately determine the risk of malignant transformation of precancerous lesions, identify more aggressive tumors, and detect disease recurrence and distant metastases could greatly improve the survival of patients with HNSCC.

In this Special Issue, we encourage the publication of scientific papers that provide new insight into genetic, molecular, and phenotypic changes in the pathogenesis of HNSCC, the tumor microenvironment, circulating tumor cells, therapeutic strategies that target important changes in tumor cells and their environment, and the use of artificial intelligence (AI) in the early diagnosis, treatment, and follow-up of patients with HNSCC.

Dr. Marko Tarle
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

  • HNSCC
  • premalignant changes
  • tumor microenvironment
  • molecular biomarkers
  • targeted therapy
  • oral tumorigenesis
  • molecular pathogenesis
  • tumor biology
  • tumor immunology

Published Papers (4 papers)

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Research

16 pages, 2593 KiB  
Article
Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models
by Pritha Mukherjee, Xin Zhou, Susana Galli, Bruce Davidson, Lihua Zhang, Jaeil Ahn, Reem Aljuhani, Julius Benicky, Laurie Ailles, Vitor H. Pomin, Mark Olsen and Radoslav Goldman
Int. J. Mol. Sci. 2024, 25(9), 4998; https://doi.org/10.3390/ijms25094998 - 03 May 2024
Abstract
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head [...] Read more.
Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored. Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
13 pages, 2926 KiB  
Article
A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma
by Matko Leović, Antonija Jakovčević, Ivan Mumlek, Irena Zagorac, Maja Sabol and Dinko Leović
Int. J. Mol. Sci. 2024, 25(9), 4630; https://doi.org/10.3390/ijms25094630 - 24 Apr 2024
Viewed by 228
Abstract
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have [...] Read more.
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well. Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
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14 pages, 3751 KiB  
Article
Potential Role of the Intratumoral Microbiota in Prognosis of Head and Neck Cancer
by Masakazu Hamada, Hiroaki Inaba, Kyoko Nishiyama, Sho Yoshida, Yoshiaki Yura, Michiyo Matsumoto-Nakano and Narikazu Uzawa
Int. J. Mol. Sci. 2023, 24(20), 15456; https://doi.org/10.3390/ijms242015456 - 22 Oct 2023
Cited by 1 | Viewed by 1525
Abstract
The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck [...] Read more.
The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck squamous cell carcinoma (HNSCC), the role of the intratumoral microbiota in the prognosis of HNSCC patients, and differentially expressed genes in tumor cells in relation to specific bacterial infections. We investigated 18 microbes at the genus level that differed between solid normal tissue (n = 22) and primary tumors (n = 154). The tissue microbiome profiles of Actinomyces, Fusobacterium, and Rothia at the genus level differed between the solid normal tissue and primary tumors of HNSCC patients. When the prognosis of groups with rates over and under the median for each microbe at the genus level was examined, rates for Leptotrichia which were over the median correlated with significantly higher overall survival rates. We then extracted 35 differentially expressed genes between the over- and under-the-median-for-Leptotrichia groups based on the criteria of >1.5 fold and p < 0.05 in the Mann–Whitney U-test. A pathway analysis showed that these Leptotrichia-related genes were associated with the pathways of Alzheimer disease, neurodegeneration-multiple diseases, prion disease, MAPK signaling, and PI3K-Akt signaling, while protein–protein interaction analysis revealed that these genes formed a dense network. In conclusion, probiotics and specific antimicrobial therapy targeting Leptotrichia may have an impact on the prognosis of HNSCC. Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
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17 pages, 3487 KiB  
Article
Necrotic Cells from Head and Neck Carcinomas Release Biomolecules That Are Activating Toll-like Receptor 3
by Tea Vasiljevic, Marko Tarle, Koraljka Hat, Ivica Luksic, Martina Mikulandra, Pierre Busson and Tanja Matijevic Glavan
Int. J. Mol. Sci. 2023, 24(20), 15269; https://doi.org/10.3390/ijms242015269 - 17 Oct 2023
Cited by 1 | Viewed by 919
Abstract
Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of [...] Read more.
Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs. Our aim was to investigate whether some of these molecules could behave as agonists of the TLR3, either in vitro or in vivo. We chose a functional approach based on reporter cell exhibiting artificial TLR3 expression and downstream release of secreted alkaline phosphatase. The production of biomolecules activating TLR3 was first investigated in vitro using three HNSCC cell lines subjected to various pronecrotic stimuli (external irradiation, serum starvation, hypoxia and oxidative stress). TLR3 agonists were also investigated in necrotic tumor fluids from five oral cancer patients and three mouse tumor grafts. The release of biomolecules activating TLR3 was demonstrated for all three HNSCC cell lines. External irradiation was the most consistently efficient stimulus, and corresponding TLR3 agonists were conveyed in extracellular vesicles. TLR3-stimulating activity was detected in the fluids from all five patients and three mouse tumor grafts. In most cases, this activity was greatly reduced by RNAse pretreatment or TLR3 blocking antibodies. Our data indicate that TLR3 agonists are consistently present in necrotic fluids from HNSCC cells and mainly made of dsRNA fragments. These endogenous agonists may induce TLR3, which might lead to a protumorigenic effect. Regarding methodological aspects, our study demonstrates that direct investigations—including functional testing—can be performed on necrotic fluids from patient tumors. Full article
(This article belongs to the Special Issue Pathogenesis and Treatments of Head and Neck Cancer)
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