Abstract

Abstract Ephrin receptor A4, or EPHA4, is a receptor tyrosine kinase that regulates neuronal stem cell maintenance and is implicated in multiple neuronal diseases. Accumulating studies have shown that EPHA4 may also play important roles in cancer progression, and pharmacological EPHA4 modulators have been tested in preclinical models as potential therapies. In breast cancer, EPHA4 is shown to regulate cancer cell invasion, stemness, and immune response. However, as breast cancer is a heterogenous disease, it is unclear whether and to what extend EPHA4 regulates these functions across different breast cancer subtypes and patient populations. To determine EPHA4 functions and potential benefit of targeting EPHA4 in different patient populations, we analyzed clinical and gene expression data from three patient cohorts: TGCA Firehose, I-SPY2 and SCAN-B. Our results show EPHA4 may be involved in angiogenesis and cell migration across all subtypes. While EPHA4 most strongly correlates with immune response in the Her2 subtype, its correlation with stemness and therapeutic resistance is more prominent in the triple negative/basal subtype. We conclude that EPHA4 inhibition maybe most beneficial for triple negative/basal patients. Citation Format: Wenchao Liu, Marsha Rosner. EPHA4 correlates with different functions and clinical outcomes in different breast cancer subtypes [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C145.

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