A deep understanding of the PTEN-Wnt/β-catenin interplay offers innovative approaches: combining PI3K/AKT and Wnt/β-catenin inhibitors to counter PTEN-driven resistance, profiling PTEN status for personalized treatments, and advancing precision medicine through PTEN-Wnt/β-catenin insights to enhance the efficiency and outcomes of cancer therapy. The gene discussed is PIK3CA; the disease is cancer.