We hypothesized that the SOX2‐OT/SOX2/GLI‐1 molecular axis is involved as a resistance mechanism in lung cancer therapy, and that LncRNA SOX2‐OT acts as an epigenetic regulator of the genetic expression of the SOX2‐OT/SOX2/GLI‐1 genes, involved in resistance mechanisms to lung cancer therapy agents, including cisplatin and EGRF‐tyrosine kinase inhibitor (TKI) erlotinib. Here, GLI1 is linked to lung carcinoma.