Precision Therapy of Head and Neck Squamous Cell Carcinoma

Precision medicine is an approach to disease prevention and treatment that takes into account genetic variability and environmental and lifestyle influences that are unique to each patient. It facilitates stratification of patient populations that vary in their susceptibility to disease and response to therapy. Shared databases and the implementation of new technology systems designed to advance the integration of this information will enable health care providers to more accurately predict and customize prevention and treatment strategies for patients. Although precision medicine has had a limited impact in most areas of medicine, it has been shown to be an increasingly successful approach to cancer therapy. Despite early promising results targeting aberrant signaling pathways or inhibitors designed to block tumor-driven processes such as angiogenesis, limited success emphasizes the need to discover new biomarkers and treatment targets that are more reliable in predicting response to therapy and result in better health outcomes. Recent successes in the use of immunity-inducing antibodies have stimulated increased interest in the use of precision immunotherapy of head and neck squamous cell carcinoma. Using next-generation sequencing, the precise profiling of tumor-infiltrating lymphocytes has great promise to identify hypoimmunogenic cancer that would benefit from a rationally designed combinatorial approach. Continued interrogation of tumors will reveal new actionable targets with increasing therapeutic efficacy and fulfill the promise of precision therapy of head and neck cancer.

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Single-Cell Spatial Proteomics Analyses of Head and Neck Squamous Cell Carcinoma Reveal Tumor Heterogeneity and Immune Architectures Associated with Clinical Outcome

10.1101/2021.03.10.434649 ◽

2021 ◽

Author(s):

Katie E. Blise ◽

Shamilene Sivagnanam ◽

Grace L. Banik ◽

Lisa M. Coussens ◽

Jeremy Goecks

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Single Cell ◽

Squamous Cell ◽

Immune Cells ◽

Spatial Organization ◽

Patient Survival ◽

Response To Therapy ◽

Neck Squamous Cell Carcinoma

ABSTRACTRecent research has provided compelling evidence that the spatial organization of cells within the tumor-immune microenvironment (TiME) of solid tumors correlates with survival and response to therapy in numerous cancer types. Here, we report results of a quantitative single-cell spatial analysis of the TiME of primary and recurrent human head and neck squamous cell carcinoma (HNSCC) tumors, that builds upon our initial longitudinal study of these same HNSCCs that annotated immune complexity at near single cell resolution. Herein, we extended multiple spatial algorithms to quantify spatial landscapes of immune cells within TiMEs. Most notably, we report that spatial compartmentalization, rather than mixing, between neoplastic tumor cells and immune cells is associated with longer patient survival, as well as revealing mesenchymal spatial cellular neighborhoods and their association with improved patient outcomes. Results reported herein are concordant with studies in other tumor types, thus indicating that cellular heterogeneity within tumors trends with spatial TiME features, and are likely prognostic for patient survival.

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Genomics and advances towards precision medicine for head and neck squamous cell carcinoma

Laryngoscope Investigative Otolaryngology ◽

10.1002/lio2.86 ◽

2017 ◽

Vol 2 (5) ◽

pp. 310-319 ◽

Cited By ~ 8

Author(s):

Carter Van Waes ◽

Omar Musbahi

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Precision Medicine ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma

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Impact of gene polymorphisms on toxicity and response rate in head and neck squamous cell carcinoma: a literature review

10.21203/rs.3.rs-1217709/v1 ◽

2022 ◽

Author(s):

hamid abbaszadeh ◽

Mahdieh Rajabi-Moghaddam

Keyword(s):

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Gene Polymorphisms ◽

Response To Therapy ◽

Neck Squamous Cell Carcinoma ◽

Response To Treatment ◽

The Impact

Abstract Advanced head and neck squamous cell carcinoma (HNSCC) is treated with radiotherapy, chemotherapy, targeted therapy or a combination of these treatments. Variations in toxicity and response to therapy are observed among patients despite similar clinicopathologic characteristics which are attributed to single nucleotide polymorphisms (SNPs). The aim of this review was to evaluate the impact of SNPs on toxicity and response to therapy in HNSCCs. A web-based search of all original articles about the impact of gene polymorphisms on toxicity and response to therapy in HNSCCs was done until September 2021 using international English language databases including Google Scholar, Scopus, PubMed and Web of science. Findings were categorized by type of treatment (radiotherapy, chemotherapy, targeted therapy, or combination therapy). In each category, studies related to growth control genes, cell proliferation, apoptosis, DNA repair genes, antioxidant and drug detoxification genes, genes of drug metabolizing enzymes, tissue remodeling genes and genes of antibody-dependent cellular cytotoxicity were discussed separately. Among studied SNPs with probable impact on toxicity and response to therapy are XRCC1, XRCC3, RAD51, Ku70, NBN, CAT, GSTP1, GSTT1, GSTM1, XPD, XPC, ERCC1, MMP3, ACSL6, EXO1, CXP2D6, FcγRIIIa, AurkA, and EGFR. Understanding gene polymorphisms will help us move toward personalized medicine and determine which patients will actually benefit from therapies for HNSCCs. By examining the SNPs, it is possible to make predictions about the patient's response to treatment or development of toxicity after treatment, and if necessary, make changes in the patient's treatment regimen.

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Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-019-54028-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Paolo Boscolo-Rizzo ◽

Enrica Rampazzo ◽

Jerry Polesel ◽

Silvia Giunco ◽

Anna Menegaldo ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Telomere Length ◽

Squamous Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Prognostic Significance ◽

Response To Therapy ◽

Neck Squamous Cell Carcinoma

AbstractA growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability.

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