Following G12Ci treatment, loss of ERK-dependent negative feedback on multiple RTKs drives adaptive G12Ci resistance and chromatin remodeling of DTPs activates multiple RTKs; HIF1α promotes transcription of genes responsible for TIC activity (71,72) and hypoxia signatures are associated with cancer stemness (42,63,82,83), DTP survival (62–64), and poor survival for patients with LUAD (73,74). This evidence concerns the gene HIF1A and cancer.