Researchers identified ZNF274 as a driver of lineage switch programs that contribute to resistance to CDK7-targeted therapy in pancreatic cancer. The report ties ZNF274 to cancer cell phenotypic plasticity and positions it as a potential vulnerability for overcoming drug resistance. The study emphasizes lineage plasticity as a mechanism cells use to evade therapy, and it suggests that controlling the ZNF274 axis could improve responses to CDK7 inhibition in patients where resistance emerges.