In contrast, high Ano1 expression, as previously reported10, increased sensitivity to afatinib, an effect that was reversed by silencing ANO1. We hypothesized that combining copanlisib (which lowers Cyclin D1 levels) with afatinib (which is more active in Ano1high cells) might be a promising therapeutic strategy for 11q13 amplified HNSCC tumors. Here, ANO1 is linked to head and neck squamous cell carcinoma.