The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies

The latest advances in the sequencing methods in head and neck squamous cell carcinoma (HNSCC) tissues have revolutionized our understanding of the disease by taking off the veil from the most frequent genetic alterations in the components of the oncogenic pathways. Among all the identified alterations, aberrancies in the genes attributed to the phosphoinositide 3-kinases (PI3K) axis have attracted special attention as they were altered in more than 90% of the tissues isolated from HNSCC patients. In fact, the association between these aberrancies and the increased risk of cancer metastasis suggested this axis as an "Achilles Heel" of HNSCC, which may be therapeutically targeted. The results of the clinical trials investigating the therapeutic potential of the inhibitors targeting the components of the PI3K axis in the treatment of HNSCC patients, either alone or in a combined-modal strategy, opened a new chapter in the treatment strategy of this malignancy. The present study aimed to review the importance of the PI3K axis in the pathogenesis of HNSCC and also provide a piece of information about the breakthroughs and challenges of PI3K inhibitors in the therapeutic strategies of the disease.