Abstract C152: Identification of therapeutic vulnerabilities from multi-omic profiling of breast cancer patient-derived xenografts of African and European ancestry
TL;DR
This work compared ADC target receptors and found high levels in many of the AA basal-like models compared to other subtypes, suggesting that this class of therapeutics should be considered as first-line therapy for these patients.
Abstract
Triple negative breast cancer (TNBC) is an aggressively metastatic and lethal subtype, representing 10-20% of diagnoses globally. This subtype occurs twice as frequently in patients of African ancestry (AA) compared to European ancestry (EA), which also contributes to significantly higher mortality. Preclinical research investigating this disparity has been hindered by a lack of experimental cellular models that were obtained from patients of different ancestries. Therefore, we are developing a set of breast cancer patient-derived xenografts (PDX) that include EA and AA patients. To characterize these new models multi-omic data have been generated. Whole Genome Sequencing was performed and single-nucleotide polymorphism analysis was used to quantitatively define the genetic ancestry; mutations, amplifications, deletions, and chromosomal changes across the PDXs were identified. Bulk RNA-sequencing data was used to identify PAM50 and TNBCtype subtypes across the groups. Proteomic analyses identified activated cellular pathways and the abundance of drug targets. We sought to contrast each data type from the AA and EA PDXs and identified distinct proteogenomic signatures and differences in drug responses across the groups. Since antibody-drug conjugates (ADC) have shown tremendous benefit to TNBC patients, including becoming a standard-of-care, we compared ADC target receptors and found high levels in many of the AA basal-like models compared to other subtypes, suggesting that this class of therapeutics should be considered as first-line therapy for these patients. Ongoing studies are focusing on defining optimal plasma-membrane targets for ADC development stratified by genetic ancestry. Joshua Haueis, Nina Dashti-Gibson, Carson J. Walker, Jadon Porch, Dylan T. Hite, Anna E. Gibson, Dhanvin R. Yajaman, Emily K. Zboril, Henos S. Negash, Jessie Tignor, Rachel K. Myrick, Amy L. Olex, Mikhail G. Dozmorov, Katarzyna M. Tyc, Nicholas T. Woods, Jose G. Trevino, J. Chuck Harrell. Identification of therapeutic vulnerabilities from multi-omic profiling of breast cancer patient-derived xenografts of African and European ancestry [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C152.