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.

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 The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment

2017 ◽  
Vol 98 (4) ◽  
pp. 868-883 ◽  
Author(s):  
Ronald Maggiore ◽  
Zachary S. Zumsteg ◽  
Karlynn BrintzenhofeSzoc ◽  
Kelly M. Trevino ◽  
Ajeet Gajra ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Older Adult ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Advanced Head ◽  
Knowledge Gaps ◽  
Assessment And Treatment ◽  
Future Direction

Molecular alterations in head and neck squamous cell carcinoma

1995 ◽  
Vol 20 (4) ◽  
pp. 291-298 ◽  
Author(s):  
L. BRON ◽  
P. MONNIER
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Alterations

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

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 p62/SQSTM1 Accumulation in Squamous Cell Carcinoma of Head and Neck Predicts Sensitivity to Phosphatidylinositol 3-Kinase Pathway Inhibitors

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90171 ◽  
Author(s):  
Wen-Liang Kuo ◽  
Marina N. Sharifi ◽  
Mark W. Lingen ◽  
Omar Ahmed ◽  
Jing Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase Pathway ◽  
Phosphatidylinositol 3

scholarly journals HPV+ and HPV- head and neck squamous cell carcinoma by analysis of tumor microenviroment

2021 ◽  
Vol 64 (3) ◽  
pp. 50-53
Author(s):  
Dumitru Brinza ◽  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Harm Reduction ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Biological Properties ◽  
Neck Squamous Cell Carcinoma ◽  
Molecular Alterations ◽  
Reduction Strategies ◽  
Tumor Microenviroment

Background: Head and neck squamous cell carcinomas (HNSCCs) are particularly aggressive epithelial tumors, that affect more than half a million patients worldwide each year. They represent a multi-factorial group of tumors caused by: alcohol, tobacco, and human papillomavirus (HPV) infections. Over the last ten years the overall 5-year survival rate of HNSCCs remained ~40–50%, inspite of significant improvement in clinical outcome of many tumor types. There are recent data that claim how some of these cells fulfill a suppressive role in the antitumor immune response. It is interesting that new clinical studies demonstrated that HPV (+) HNSCCs were among tumors with the highest immune infiltrates, while HPV (-) presented a reduced number of immune infiltrating cells. Conclusions: Recent researches prove that tumor microenvironment of HNSCC has an important role in tumor progression, aggressivity, metastasis process, in addition to genetic aberrations and molecular alterations of cancer cells. New researches in stromal composition of the HNSCC may be useful in understanding of mechanisms of different responses to therapy, also can be used as a target for therapeutic purposes. Cancer-associated fibroblasts and immune cells, as well as their products found in neck squamous cell carcinoma significantly influence the biological properties of this tumor. Smoking is one of the risk factors of occurrence of most HPV-associated tumors. Promoting smoking cessation should become an essential contributor to the treatment of cancer in all oncologic pathologies. In cases when patients can’t quit smoking completely within the shortest possible period of time, doctors should focus on harm reduction strategies – tobacco harm reduction.

Sign in / Sign up

Export Citation Format

Share Document