The finding that cyclin D alone did not fully mimic the phenotype of AMBRA1 loss with respect to CDK4/6 inhibition may point toward additional changes beyond the mere induction of cyclin D,2 e.g., the cyclin D–CDK2 complexes or the induction of MYC family members.3 Lastly, the impact of AMBRA1 seems to depend on the genetic background: AMBRA1 correlates with survival in KRAS G12-mutant lung cancer, but not in KRAS wildtype or EGFR-driven lung cancer, which may reflect a more complex interplay of these pathways.2 This evidence concerns the gene EGFR and lung cancer.