The Development of Differentiation-Based Therapy for Breast Cancer Using EDAR and XEDAR Signalling Pathways: A Conceptual Framework

Breast cancer remains one of the most challenging cancers to treat, often due to evolving resistance to conventional therapies. This article presents a conceptual framework for differentiation therapy that exploits the EDAR and XEDAR signaling pathways. A two-phase therapeutic strategy involving epigenetic restoration of XEDAR expression and synthetic ligands to activate these pathways is described. The proposed approach targets patient subgroups with aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC), and those exhibiting high XEDAR promoter methylation. By focusing on cellular differentiation rather than cytotoxicity, this therapy could transform aggressive malignancies into more manageable chronic conditions. Potential technical, biological, and clinical challenges are discussed alongside proposed solutions to overcome them.