Translational research in head and neck cancer: Molecular and immunological updates

Kumai, Takumi; Shinomiya, Hirotaka; Shibata, Hirofumi; Takahashi, Hideaki; Kishikawa, Toshihiro; Okada, Ryuhei; Fujieda, Shigeharu; Sakashita, Masafumi

doi:10.1016/j.anl.2023.08.006

Auris Nasus Larynx

2024

DOI: 10.1016/j.anl.2023.08.006

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Translational research in head and neck cancer: Molecular and immunological updates

Takumi Kumai,

Hirotaka Shinomiya,

Hirofumi Shibata

et al.

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Cited by 6 publications

References 120 publications

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Head and neck cancer: pathogenesis and targeted therapy

Liu,

Zhang,

Wen

et al. 2024

MedComm

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Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early‐stage HNC. For recurrent or metastatic (R/M) HNC, the first‐line treatment is platinum‐based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody–drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.

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Head and neck cancer: pathogenesis and targeted therapy

Liu,

Zhang,

Wen

et al. 2024

MedComm

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Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries

Sharaky,

Dokla,

Abdel-Aziz

2025

Toxicology in Vitro

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Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer

Pan,

Fei,

Wang

et al. 2024

Front. Immunol.

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BackgroundCell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear.MethodsData from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model.ResultsT cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10, DDX19A, NDFIP1, PCMT1, HPRT1, SLC2A3, EFNB2, HK1, BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription.ConclusionThe CDRscore model could be utilized as a powerful prognostic indicator for HNC.

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Translational research in head and neck cancer: Molecular and immunological updates

Cited by 6 publications

References 120 publications

Head and neck cancer: pathogenesis and targeted therapy

Head and neck cancer: pathogenesis and targeted therapy

Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries

Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer

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