For example, studies with patient-derived organoids, xenografts, and lineage tracing have shown high plasticity in CRC, where tumors can persist after CSC ablation through reacquisition of stem-like traits independent of niche signals.180–182 Similarly, in lung adenocarcinoma, oncogenic signaling as elicited by KRAS proto-oncogene, GTPase (KRAS) mutations initiate lineage reprogramming by activating ERK signaling.183 Extrinsic factors, including microenvironmental cues and therapeutic stress, can also drive cellular plasticity. This evidence concerns the gene KRAS and lung adenocarcinoma.