Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have transformed the treatment landscape for hormone receptor+ (HR+) breast cancer. However, their long-term efficacy is limited by acquired resistance, and CDK4/6i monotherapy remains ineffective in triple-negative breast cancer (TNBC). Here, we demonstrate that dual inhibition of CDK4/6 and CDK7 is a promising strategy to overcome therapeutic resistance in both HR+ and TNBC models. Kinetic analyses revealed that CDK7 inhibitors (CDK7i) primar...