Head and neck squamous cell carcinoma (
HNSCC) is the sixth most common
malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat
HNSCC. Recent deep sequencing of the
HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this
malignancy. Although a large variety of specific molecules were found altered in each individual
tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in
cancer initiation and progression. In turn, targeting of mTOR may represent a precision therapeutic approach for
HNSCC. Indeed, mTOR inhibition exerts potent anti-
tumor activity in
HNSCC experimental systems, and mTOR targeting clinical trials show encouraging results. However, advanced
HNSCC patients may exhibit unpredictable drug resistance, and the analysis of its molecular basis suggests that co-targeting strategies may provide a more effective option. In addition, although counterintuitive, emerging evidence suggests that mTOR inhibition may enhance the anti-
tumor immune response. These new findings raise the possibility that the combination of
mTOR inhibitors and immune oncology agents may provide novel precision therapeutic options for
HNSCC.