The combination of Copanlisib with Cetuximab is now evaluated in a phase 1 and 2 trial in metastatic HNSCC patients with PIK3CA mutations or amplifications and/or PTEN loss as PIK3CA mutations and amplifications are associated with resistance to Cetuximab therapy (see Table 3) [69]. Here, PIK3CA is linked to head and neck squamous cell carcinoma.