scholarly journals Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 22203-22217 ◽  
Author(s):  
Yi Cai ◽  
Sonam Dodhia ◽  
Gloria H. Su
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma

scholarly journals Role of Phosphatidylinositol-3-Kinase Pathway in Head and Neck Squamous Cell Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Li Du ◽  
Jingping Shen ◽  
Andrew Weems ◽  
Shi-Long Lu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Phosphatidylinositol 3 Kinase ◽  
Molecular Alterations ◽  
Future Direction ◽  
Phosphatidylinositol 3

Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most frequently observed molecular alterations in many human malignancies, including head and neck squamous cell carcinoma (HNSCC). A growing body of evidence demonstrates the prime importance of the PI3K pathway at each stage of tumorigenesis, that is, tumor initiation, progression, recurrence, and metastasis. Expectedly, targeting the PI3K pathway yields some promising results in both preclinical studies and clinical trials for certain cancer patients. However, there are still many questions that need to be answered, given the complexity of this pathway and the existence of its multiple feedback loops and interactions with other signaling pathways. In this paper, we will summarize recent advances in the understanding of the PI3K pathway role in human malignancies, with an emphasis on HNSCC, and discuss the clinical applications and future direction of this field.

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

Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma

2015 ◽  
pp. 123-128 ◽  
Author(s):  
Pedro Henrique Isaacsson Velho ◽  
Gilberto Castro ◽  
Christine H. Chung
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Anticancer Agents ◽  
Neck Region ◽  
Hpv Infection ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Preclinical Data

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.

Antitumor activity of tipifarnib and PI3K pathway inhibitors in HRAS-associated head and neck squamous cell carcinoma

2020 ◽  
Vol 138 ◽  
pp. S43-S44
Author(s):  
F. Burrows ◽  
M. Shivani ◽  
Z. Wang ◽  
S. Chan ◽  
M. Gilardi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Antitumor Activity ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma

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.

Identification of factors related to immunotherapy prognosis in patients with advanced head and neck squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18003-e18003
Author(s):  
Lin Zhang ◽  
Xuanli Xu ◽  
Dandan Ren ◽  
Lijia Wu ◽  
Xiaoli Gong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cells ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Dismal Prognosis

e18003 Background: Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Anti-PD1/PD-L1 checkpoint inhibitors have shown survival benefit for the treatment on HNSCC, and are better tolerated than chemotherapy. Unfortunately, the response rate of immunotherapy is low for advanced HNSCC. Therefore, the identification of predictive biomarkers of response to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit from immunotherapy. Methods: The present study included 44 patients with advanced HNSCC who received anti-PD-1 immunotherapy. Follow-up was available for them. Primary tumor tissues and matched blood samples were collected. Genome profiles were analyzed using a designed 543-gene panel based on NGS, and were available on 39 of 44 patients. Profiles of infiltrating immune cells were available for 44 patients. The infiltrating intensity of PD-1, PD-L1, CD8, CD68 and CD57 positive cells were assessed by multiplex immunohistochemistry. Results: The most frequently mutated genes were TP53 (79%), CDKN2A (33%), NOTCH1 (21%), CASP8 (13%) and PIK3CA (10%). Patients with mutations in the PI3K pathway showed a trend of longer OS (P = 0.06). Moreover, the TMB-high group showed significant superior OS than the TMB-low group (p = 0.0018). PD-L1 expression was positively correlated with CD8 expression within stroma, and PD-1 expression correlated significantly with PD-L1 and CD8 expression within both tumor and stroma areas. In addition, tumor/stromal PD-L1 and PD-1 expression were both associated with better OS (P < 0.05). Prolonged OS was also observed in patients with more tumor and stromal infiltration of CD8+ cells, CD8+PD-L1+ cells, CD68+ macrophages, or nature killer (NK, CD57+) cells. Conclusions: Higher TMB, PD-L1 expression, as well as the infiltration of immune cells within both tumor and stromal area might serve as favorable prognostic markers in advanced HNSCC patients treated with anti-PD-1 immunotherapy.

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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