Antibody–drug conjugates targeting RON receptor tyrosine kinase as a novel strategy for treatment of triple-negative breast cancer.

• Aberrant RON expression is a pathogenic feature in breast cancer including TNBC. • Antibody-drug conjugates targeting RON for TNBC therapy is a novel strategy. • Anti-RON ADCs eradicate TNBC xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. • The efficacy of anti-RON ADCs warrants their transition into clinical trials. Treatment of triple-negative breast cancer (TNBC) is a challenge to oncologists. Currently, the lack of effective therapy has fostered a major effort to discover new targets and therapeutics to combat this disease. The recepteur d'origine nantais (RON) receptor has been implicated in the pathogenesis of TNBC. Clinical studies have revealed that aberrant RON expression is crucial in regulating TNBC malignant phenotypes. Increased RON expression also has prognostic value for breast cancer progress. These features provide the rationale to target RON for TNBC treatment. In this review, we discuss the importance of RON in TNBC tumorigenesis and the development of anti-RON antibody–drug conjugates (ADCs) for clinical application. The findings from preclinical studies lay the foundation for clinical trials of this novel biotherapeutic for TNBC therapy. Discovery of novel targets and therapeutics, such as antibody–drug conjugates, targeting RON hold the promise to effectively combat triple-negative breast cancer in the future. [ABSTRACT FROM AUTHOR]