Targeting CD44v3 rescues Entrectinib response in brain metastasis of triple negative breast cancer overexpressing TrkA

Tropomyosin receptor kinase A (TrkA, encoded by NTRK1 ) is frequently overexpressed in solid tumors, 1 including breast cancer, 2 and is associated with poor prognosis and therapeutic resistance. While FDA-approved Trk inhibitors such as Entrectinib show remarkable efficacy against NTRK gene fusions, their activity is limited in tumors harboring Trk overexpression [ https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212725Orig1s000,%20212726Orig1s000MultidisciplineR.pdf ]. This clinical discrepancy highlights an unresolved mechanism of primary resistance in breast cancer and underscores the need for strategies to overcome it.