Targeting the Tumor Microenvironment through mTOR Inhibition and Chemotherapy as Induction Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: The CAPRA Study.

Mammalian target of rapamycin (mTOR) regulates cellular functions by integrating intracellular signals and signals from the tumor microenvironment (TME). The PI3K-AKT-mTOR pathway is activated in 70% of head and neck squamous cell carcinoma (HNSCC) and associated with poor prognosis. This phase I-II study investigated the effect of mTOR inhibition using weekly everolimus (30 mg for dose level 1, 50 mg for dose level 2) combined with weekly induction chemotherapy (AUC2 carboplatin and 60 mg/m paclitaxel) in treatment-naïve patients with locally advanced T3-4/N0-3 HNSCC.

Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck cancer cell lines.

Purpose: Recent data suggested that combining targeted therapies with chemotherapy may counteract drug resistance. Activation of the PI3K/AKT/mTOR pathway downstream to kinase receptors, such as EGFR, was found in 57-81% of head and neck squamous cell carcinoma (HNSCC), and was eventually associated with a loss of PTEN function. mTOR was shown to modulate cell proliferation, apoptosis, invasion, and angiogenesis.