Therapeutic Implications of the Genetic Landscape of Head and Neck Cancer

Cho, Janice; Johnson, Daniel E.; Grandis, Jennifer R.

doi:10.1016/j.semradonc.2017.08.005

Cited by 24 publications

(22 citation statements)

References 97 publications

(150 reference statements)

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“…Among the key prognostic markers for survival, epidermal growth factor receptor (EGFR), cyclin D1(CCND1), ERCC1, p16, human papillomavirus (HPV), and B‐cell lymphoma‐extra large (Bcl‐xL)/Bcl‐2, as well as the amplification of genes including EMS1 , FGFR1 , and CCND1 have demonstrated some evidence in clinical trials. Others are slower to advance in clinical development because of unconvincing data and few published studies; for example, acetylcholinesterase(AchE), SNPs of specific genes, glutathione S‐transferase (GST), CD44, amplification of specific genes, hypoxic markers, KLK‐6, and MDA‐7/IL‐24; although, this does not preclude them from future investigations and clinical utility.…”

Section: Biomarkers In Hnscc Tumor Tissuesmentioning

confidence: 99%

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Hsieh

Wang

et al. 2019

Head & Neck

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Background Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. Methods Recent, relevant peer‐reviewed evidence were critically reviewed and summarized. Results This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. Conclusion Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.

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Section: Biomarkers In Hnscc Tumor Tissuesmentioning

confidence: 99%

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Hsieh

Wang

et al. 2019

Head & Neck

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“…The gene expression subtypes proposed by TCGA group are atypical, classical, mesenchymal and basal [9]. In addition, among the most recognized common mutations by these studies are NOTCH1, TP53, CDKN2A, PIK3CA and NSD1 [[9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of radiomic signatures of head and neck squamous cell carcinoma molecular features and subtypes

Chao

Cintra

Brennan³

et al. 2019

EBioMedicine

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Background: Radiomics-based non-invasive biomarkers are promising to facilitate the translation of therapeutically related molecular subtypes for treatment allocation of patients with head and neck squamous cell carcinoma (HNSCC). Methods: We included 113 HNSCC patients from The Cancer Genome Atlas (TCGA-HNSCC) project. Molecular phenotypes analyzed were RNA-defined HPV status, five DNA methylation subtypes, four gene expression subtypes and five somatic gene mutations. A total of 540 quantitative image features were extracted from pretreatment CT scans. Features were selected and used in a regularized logistic regression model to build binary classifiers for each molecular subtype. Models were evaluated using the average area under the Receiver Operator Characteristic curve (AUC) of a stratified 10-fold cross-validation procedure repeated 10 times. Next, an HPV model was trained with the TCGA-HNSCC, and tested on a Stanford cohort (N = 53). Findings: Our results show that quantitative image features are capable of distinguishing several molecular phenotypes. We obtained significant predictive performance for RNA-defined HPV+ (AUC = 0.73), DNA methylation subtypes MethylMix HPV+ (AUC = 0.79), non-CIMP-atypical (AUC = 0.77) and Stem-like-Smoking (AUC = 0.71), and mutation of NSD1 (AUC = 0.73). We externally validated the HPV prediction model (AUC = 0.76) on the Stanford cohort. When compared to clinical models, radiomic models were superior to subtypes such as NOTCH1 mutation and DNA methylation subtype non-CIMP-atypical while were inferior for DNA methylation subtype CIMP-atypical and NSD1 mutation. Interpretation: Our study demonstrates that radiomics can potentially serve as a non-invasive tool to identify treatment-relevant subtypes of HNSCC, opening up the possibility for patient stratification, treatment allocation and inclusion in clinical trials.

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“…Head and neck squamous cell carcinoma (HNSCC) is the leading histology-type malignancy in the upper aerodigestive tract and is characterized by a marked propensity of invasion and cervical lymph node metastasis associated with poor outcomes. Despite advancements in multimodality therapy surgery, radiation, chemotherapy, and recent progress in immunotherapy, HNSCC often remains fatal, necessitating new and more efficacious therapeutic strategies to enhance the HNSCC survival (1).…”

Section: Introductionmentioning

confidence: 99%

CD147 mediates transforming growth factor‑β1‑induced epithelial‑mesenchymal transition and cell invasion in squamous cell carcinoma of the tongue

et al. 2019

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Epithelial-mesenchymal transition (EMT) is a physiological process in which epithelial cells attain the motile and invasive characteristics of mesenchymal cells, which results in the development of increased migratory and invasive cell behavior, serving as a vital mechanism of cancer progression. Hence, controlling the EMT for cancer treatment, including head and neck squamous cell carcinoma (HNSCC), is imperative. Among EMT-associated factors, transforming growth factor-β (TGF-β) is a well-established potent inducer. Recent research has revealed that CD147, a member of the immunoglobulin superfamily, promotes the EMT. However, the role of CD147 in the EMT and the following tumorigenicity in HNSCC has not been completely elucidated. This study aims to investigate the role of CD147 in the EMT and related tumorigenicity in HNSCC. The present study used two HNSCC cell lines, SAS and FaDu, for in vitro studies. In HNSCC cells, TGF-β1 induced spindle-shaped morphological changes, and western blot analysis revealed that TGF-β1 induced changes in EMT markers, downregulation of vimentin, and upregulation of E-cadherin, yet increased CD147. In addition, TGF-β1 increased cell migration in HNSCC cells. However, a TGF-β1-induced alteration in EMT makers was attenuated with CD147 silencing by small interfering RNA (siRNA) in SAS cells. In addition, the TGF-β1-induced cell invasion of SAS was attenuated with CD147 silencing. In conclusion, the present study suggests that CD147 mediates TGF-β1-induced EMT and tumorigenicity in HNSCC. Hence, CD147 may serve as a vital therapeutic target in HNSCC.

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Therapeutic Implications of the Genetic Landscape of Head and Neck Cancer

Cited by 24 publications

References 97 publications

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Development and validation of radiomic signatures of head and neck squamous cell carcinoma molecular features and subtypes

CD147 mediates transforming growth factor‑β1‑induced epithelial‑mesenchymal transition and cell invasion in squamous cell carcinoma of the tongue

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