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

Abstract

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.

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling

“…EGFR is a known contributor to HNSCC, ESCC, and breast cancer tumorigenesis and is one the most important therapeutic targets in HNSCC. High levels of EGFR and the activation of PI3K signaling have been correlated with poor prognosis in HNSCC and breast cancer, and the prognostic significance of EGFR phosphorylation has been described recently for both cancer types (51)(52)(53)(54). However, EGFR amplification and activating mutations are rare and account for only a small subset of HNSCC cases (55,56).…”

Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck

“…Numerous mutations or alterations in the PI3K pathway have now been identified in human SCCHN, at the level of both gene expression and function (Table 2) [29]. These genes include, but are not limited to: PIK3CA, PIK3CD, PTEN, PDK1, AKT, and mTOR [8,[30][31][32][33][34][35]. Mutations and copy number alterations of PI3K pathway components, including PIK3CA amplifications and PTEN inactivation by loss or inactivation of gene copy, are particularly prevalent in HPV-positive tumors [36].…”

A Comprehensive Evaluation of Biomarkers Predictive of Response to PI3K Inhibitors and of Resistance Mechanisms in Head and Neck Squamous Cell Carcinoma

“…Pathway components are frequently altered in cancer cells, leading to pathway activation and poor prognosis ( 6 , 7 ). In HNSCC specifically, there are gain-of-function mutations in PIK3CA (6-13%), LOH of PTEN (8%), reduced PTEN protein expression (30%), PIK3CA gene overexpression (52%), PIK3CA amplification (20%), PIK3CG mutations (4%), and inactivating mutations in PTEN (4%) ( 2-6 , 8-10 ). AKT1 , PIK3R1 , and mTOR mutations occur rarely ( 5 ).…”