Loss of ARID1A Activates ANXA1 , which Serves as a Predictive Biomarker for Trastuzumab Resistance

PURPOSE: Despite the substantial progress in the development of targeted anticancer drugs, treatment failure due to primary or acquired resistance is still a major hurdle in the effective treatment of most advanced human cancers. Understanding these resistance mechanisms will be instrumental to improve personalized cancer treatment. EXPERIMENTAL DESIGN: breast cancer trials FinHer and Responsify were used to validate our findings in patient series. RESULTS: breast cancer patient series that high ANXA1 expression is associated with resistance to adjuvant trastuzumab-based therapy. CONCLUSIONS: Our findings provide a rationale for why tumors accumulate ARID1A mutations and identify high ANXA1 expression as a predictive biomarker for trastuzumab-based treatment. Our findings also suggest strategies to treat breast cancers with elevated ANXA1 expression. Clin Cancer Res; 22(21); 5238-48.