Harnessing AI to Reveal CTNNB1’s Central Role in Breast Cancer Progression and Drug Discovery

CTNNB1 encodes β-catenin, a multifunctional protein critically involved in cell adhesion and canonical Wnt signaling, fundamental for cellular homeostasis, gene regulation, and proliferation. In breast cancer, aberrant activation of the Wnt/β-catenin pathway is commonly observed, particularly in aggressive subtypes such as triple-negative breast cancer (TNBC), where elevated β-catenin correlates with high tumor grade and poor prognosis. Unlike colorectal cancer, CTNNB1 mutations are rare in breast cancer; pathway dysregulation is driven primarily by alterations in Wnt ligands, receptors, and loss of E-cadherin-mediated β-catenin sequestration. CTNNB1 signaling also supports breast cancer stem cell maintenance, metastasis, and therapy resistance, underscoring its therapeutic relevance. Current clinical strategies targeting this pathway include PORCN inhibitors, direct β-catenin interaction inhibitors, and natural compounds, although challenges remain in patient selection and toxicity management. Emerging immunotherapies and combination regimens offer promising avenues. Multi-omics and network analyses reaffirm CTNNB1 as a master regulator with robust biomarker strength and central network involvement, particularly in oncogenic processes. This evolving landscape highlights CTNNB1 as a high-priority target for precision oncology in breast cancer.