Kinase signaling pathways are among the most important therapeutic targets in breast cancer, yet many patients fail to benefit from existing kinase inhibitors because the molecular determinants of drug response remain poorly understood. Our laboratory combines CRISPR genome engineering, functional genomics, phosphoproteomics, and clinicogenomic analyses to uncover the genetic and signaling features that govern sensitivity and resistance to targeted therapies. Using high-throughput perturbation screens, we systematically identify kinase dependencies and therapeutic vulnerabilities across breast cancer models. We integrate these functional studies with genomic data from patient tumors to define how oncogenic alterations reshape kinase signaling and influence treatment response. By identifying predictive biomarkers and rational drug combinations, our work aims to accelerate the development of more effective precision therapies for breast cancer.