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The phosphatidyl-inositol 3-kinase/Akt/ mammalian target of rapamycin pathway as a therapeutic target in head and neck cancer

Saad A Khan & Julie E Bauman

Phosphatidyl-inositol 3-kinase/Akt/mammalian target of rapamycin pathway (PI3K/ Akt/mTOR) is a critical signal transduction pathway in mammalian cellular biology, and is important to energy homeostasis, growth and survival. Activation of the pathway is an early event in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. Moreover, PI3K/Akt/mTOR is the most commonly mutated pathway in HNSCC, with striking prevalence in human papillomavirus (HPV) associated disease. Genomic gain of function can also be conferred by PIK3CA gene amplification or loss of phosphatase and tensin homolog, the negative regulator of PI3K. Given the importance of PI3K/ Akt/mTOR signaling across the neoplastic spectrum, pathway inhibitors are of unique interest in HNSCC. This review will summarize current knowledge, highlight differences in HPV(+) and HPV(-) disease and discuss therapeutic agents in various phases of clinical development.