Therefore, we hypothesize that SMAD3 secreted by cancer-associated fibroblasts (CAFs) may regulate the downstream PI3K/Akt signaling pathway through its interaction with ITGA6, thereby affecting cell proliferation and survival and consequently influencing the sensitivity of non-small cell lung cancer (NSCLC) to radiation therapy. The gene discussed is ITGA6; the disease is non-small cell lung carcinoma.