Cutting-edge cancer studies expose new molecular targets and strategies to overcome treatment resistance. St. Jude and Dana-Farber teams identify histone acetyltransferases MOZ/KAT6A and HBO1/KAT7 as vulnerabilities in aggressive pediatric AML driven by NUP98 fusions. A new organoid model replicates residual colorectal cancer stem cells post-chemotherapy, offering insights into relapse. CHEK2 gene’s role in DNA repair deficiency potentially enhances immunotherapy efficacy in solid tumors. Advanced genetic barcoding techniques elucidate phenotype evolution under drug pressure, potentially informing personalized treatment paradigms.