Abstract
The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.
Highlights
The phosphoinositide 3-kinase (PI3K) signaling pathway is of particular importance in head and neck squamous cell carcinoma (HNSCC), as it is the most frequently mutated pathway [1, 2]
Copanlisib in combination with cetuximab is being evaluated in phase 1 and phase 2 trials in patients with recurrent and/or metastatic HNSCC harboring a PI3KCA mutation/amplification and/or a PTEN loss
In a PIK3CA-dependent murine xenograft model, alpelisib showed significant dose-dependent inhibition of tumor growth and a favorable safety profile [75]. These results suggest that alpelisib is a promising agent for treating tumors with PIK3CA mutations
Summary
The phosphoinositide 3-kinase (PI3K) signaling pathway is of particular importance in head and neck squamous cell carcinoma (HNSCC), as it is the most frequently mutated pathway [1, 2]. The PI3K/Akt/mTOR pathway is activated in many types of cancers and has been demonstrated to contribute to treatment resistance [5]. In the majority of the clinical trials, PI3K/ Akt/mTOR inhibitors are used in combination with other agents or radiation with the goal of achieving a synergistic www.impactjournals.com/oncotarget effect [65].
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