Advanced estrogen receptor-positive (ER+) breast cancer often develops resistance to current treatments that combine endocrine therapy with CDK4/6 or PI3K/AKT/mTOR inhibitors. Once this happens, treatment options are limited, and new strategies are urgently needed. Research shows that these pathways work together to drive tumor growth, suggesting that blocking all three pathways at the same time may provide stronger and longer-lasting responses.
In this project, we will study how combined targeting of the ER, CDK4/6, and PI3K/AKT/mTOR pathways can overcome resistance and improve treatment outcomes. Using patient-derived organoids developed from tumor samples, we will analyze how these drug combinations work at the cellular and molecular levels. We will also use cutting-edge single-cell and spatial transcriptomic technologies to uncover new mechanisms of resistance and identify additional therapeutic targets. Our goal is to develop optimized, personalized treatment strategies for patients with advanced ER+ breast cancer who no longer respond to current combination therapies.