TP53 and head and neck squamous cell carcinoma: Furthermore, another interesting possibility of specific relevance to HNSCC is that REDD1, SESTRIN1 and SESTRIN2, all downstream targets of p53 and negative regulators of mTOR, are presumably disabled in more than 50% of HNSCC harboring TP53 mutations what could result in mTOR activation in the absence of any other obvious genomic alteration of the PI3K pathway.