biostudies-literatureTorres-Adorno AMU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)U.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHS2135-2150https://www.ebi.ac.uk/biostudies/studies/S-EPMC6430703biostudies-literatureUnknown38(12)Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, currently lacks effective targeted therapy options. Eicosapentaenoic acid (EPA), an omega-3 fatty acid and constituent of fish oil, is a common supplement with anti-inflammatory properties. Although it is not a mainstream treatment, several preclinical studies have demonstrated that EPA exerts anti-tumor activity in breast cancer. However, against solid tumors, EPA as a monotherapy is clinically ineffective; thus, we sought to develop a novel targeted drug combination to bolster its therapeutic action against TNBC. Using a high-throughput functional siRNA screen, we identified Ephrin type-A receptor 2 (EPHA2), an oncogenic cell-surface receptor tyrosine kinase, as a therapeutic target that sensitizes TNBC cellOncogeneEicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux.PMC6430703R01CA123318P30 CA016672R01 CA123318R35 CA197707Tan LFan YYVitrac HEckhardt BLLevental KRQi YChapkin RSYang PUeno NTTorres-Adorno AMfalseEicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux.Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, currently lacks effective targeted therapy options. Eicosapentaenoic acid (EPA), an omega-3 fatty acid and constituent of fish oil, is a common supplement with anti-inflammatory properties. Although it is not a mainstream treatment, several preclinical studies have demonstrated that EPA exerts anti-tumor activity in breast cancer. However, against solid tumors, EPA as a monotherapy is clinically ineffective; thus, we sought to develop a novel targeted drug combination to bolster its therapeutic action against TNBC. Using a high-throughput functional siRNA screen, we identified Ephrin type-A receptor 2 (EPHA2), an oncogenic cell-surface receptor tyrosine kinase, as a therapeutic target that sensitizes TNBC cell2019-01-01T00:00:00Z2019 Mar2026-05-03T22:04:52.462Z2019-06-06T23:24:39ZS-EPMC64307033045935810.1038/s41388-018-0569-5