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management of head and neck squamous cell carcinomas (HNSCC) include anti-Epidermal Growth Factor Receptor (EGFR) antibodies and radiotherapy, but resistance emerges in most patients. RAS mutations lead to primary resistance to EGFR blockade in metastatic colorectal cancer but are infrequent in HNSCC, suggesting that other mechanisms are implicated. Since hypoxia and Hypoxia Inducible Factor-1 (HIF-1) have been associated with treatment failure and tumor progression, we hypothesized that EGFR/mammalian Target Of Rapamycin (mTOR)/HIF-1 axis inhibition could radiosensitize HNSCC.

Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC