To this end, a panel of eight 3D lrECM-embedded HNSCC models was treated with Alpelisib (selective PI3Kα inhibitor), Copanlisib (pan-PI3K inhibitor), AZD8186 (selective PI3Kβ/δ inhibitor), or Idelalisib (selective PI3Kδ inhibitor) in combination with Cisplatin and/or 6 Gy X-rays (Fig. 1A and S1A, B). Here, PIK3CA is linked to head and neck squamous cell carcinoma.