scholarly journals Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma

2018 ◽  
Vol 118 (4) ◽  
pp. 509-521 ◽  
Author(s):  
Hailong Ma ◽  
Shufang Jin ◽  
Wenyi Yang ◽  
Ge Zhou ◽  
Mei Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Interferon Alpha ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Antitumour Activity ◽  
Neck Squamous Cell Carcinoma

scholarly journals Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 717 ◽  
Author(s):  
Julia K. Harms ◽  
Tet-Woo Lee ◽  
Tao Wang ◽  
Amy Lai ◽  
Dennis Kee ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Antitumour Activity ◽  
Neck Squamous Cell Carcinoma ◽  
Significant Activity ◽  
Tumour Hypoxia ◽  
Patient Derived Xenograft ◽  
Pdx Models

Tumour hypoxia is a marker of poor prognosis and failure of chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC), providing a strategy for therapeutic intervention in this setting. To evaluate the utility of the hypoxia-activated prodrug evofosfamide (TH-302) in HNSCC, we established ten early passage patient-derived xenograft (PDX) models of HNSCC that were characterised by their histopathology, hypoxia status, gene expression, and sensitivity to evofosfamide. All PDX models closely resembled the histology of the patient tumours they were derived from. Pimonidazole-positive tumour hypoxic fractions ranged from 1.7–7.9% in line with reported HNSCC clinical values, while mRNA expression of the Toustrup hypoxia gene signature showed close correlations between PDX and matched patient tumours, together suggesting the PDX models may accurately model clinical tumour hypoxia. Evofosfamide as a single agent (50 mg/kg IP, qd × 5 for three weeks) demonstrated antitumour efficacy that was variable across the PDX models, ranging from complete regressions in one p16-positive PDX model to lack of significant activity in the three most resistant models. Despite all PDX models showing evidence of tumour hypoxia, and hypoxia being essential for activation of evofosfamide, the antitumour activity of evofosfamide only weakly correlated with tumour hypoxia status determined by pimonidazole immunohistochemistry. Other candidate evofosfamide sensitivity genes—MKI67, POR, and SLFN11—did not strongly influence evofosfamide sensitivity in univariate analyses, although a weak significant relationship with MKI67 was observed, while SLFN11 expression was lost in PDX tumours. Overall, these data confirm that evofosfamide has antitumour activity in clinically-relevant PDX tumour models of HNSCC and support further clinical evaluation of this drug in HNSCC patients. Further research is required to identify those factors that, alongside hypoxia, can influence sensitivity to evofosfamide and could act as predictive biomarkers to support its use in precision medicine therapy of HNSCC.

scholarly journals Recent Advances in Biomarkers and Potential Targeted Therapies in Head and Neck Squamous Cell Carcinoma

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Eric J. Yavrouian ◽  
Uttam K. Sinha
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Neck Squamous Cell Carcinoma ◽  
Oncogenic Viruses ◽  
Upper Aerodigestive Tract

Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor of the upper aerodigestive tract with no significant change in treatment modality or improvement in survival over the last several decades. Biomarkers are important biological molecules that can be utilized in tumor detection, prognosis, and as targeted therapies. There are several important biomarkers and potential targets in the forefront, including biomarkers of tumorigenesis, signal transduction molecules, proteins involved in angiogenesis, and oncogenic viruses. The clinical applications of these biomarkers are in various states from in vitro and in vivo models, phase II and III clinical trials, to accepted modes of treatment in patients with HNSCC. Given the potential improvement in prognosis that biomarkers and their targeted therapies may have on the treatment of HNSCC, their investigation is both important and essential.

scholarly journals Interferon-alpha promotes immunosuppression through IFNAR1/STAT1 signalling in head and neck squamous cell carcinoma

2018 ◽  
Vol 120 (3) ◽  
pp. 317-330 ◽  
Author(s):  
Hailong Ma ◽  
Wenyi Yang ◽  
Liming Zhang ◽  
Shuli Liu ◽  
Mei Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Interferon Alpha ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma

scholarly journals Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review

2021 ◽  
Vol 14 (1) ◽  
pp. 50-60
Author(s):  
Uzdan Uz ◽  
Görkem Eskiizmir
Keyword(s):  
Systematic Review ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Interleukin 6 ◽  
Randomized Clinical Trials ◽  
Elevated Serum ◽  
Neck Squamous Cell Carcinoma

Interleukin-6 (IL-6) is a proinflammatory cytokine which plays an important role in several regulatory mechanisms of cancer. Moreover, experimental and clinical studies have reported that IL-6 targeted therapies might provide significant benefits for cancer treatment. The purpose of this systematic review is to evaluate IL-6 activity in patients with head and neck squamous cell carcinoma (HNSCC). A systematic review of the association between serum, saliva and tumor IL-6 and HNSCC was developed on PubMed/Medline in the publication range from January 1995 to January 2019. Our literature analysis demonstrated that overexpression and elevated serum and/or saliva IL-6 concentrations in patients with HNSCC are related to poor survival and oncological outcomes. Although there is a correlation between IL-6 concentrations and tumorigenicity, it is noteworthy that IL-6 targeted therapies are generally performed in vitro and in experimental studies. Therefore, prospective, randomized clinical trials are required that focus on IL-6 targeted therapies for the treatment of HNSCC.

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