Abstract 3990: Characterization of triple negative breast cancer organoids from diverse ethnic populations

Abstract

Abstract Introduction: Triple negative breast cancer (TNBC) among women with African ancestry has been shown to be more prevalent than in women of European ancestry. However, the root cause for this disparity is not fully understood. We have previously shown that the gene expression in the breast cancer stem cells of TNBC tumors differs based on Western sub-Saharan ancestry. Tumor organoids are three-dimensional structures that are derived from tumor cells and are able to mimic the organization and function of the organ of origin. Organoids are, therefore, valuable tools for studying complex interactions in cancer biology. To have a better understand of how differential gene expression based on ancestry affects aggressiveness of TNBC, we are developing and characterizing patient derived xenografts (PDXs) and organoids from TNBC tumors derived from African (Ghanaian), European American and AA populations. Objective: The objective of the study is to develop and characterize PDXs from TNBC tumors that will serve as a renewable source for studying how differential gene expression based on ancestry affects aggressiveness of TNBC among AA. Methods: Fresh tumors from continental Africa (Ghana), European American, and African American (Henry Ford Hospital) were collected from consenting patients during surgery. The tumors were then implanted in mice and organoids developed from the resulting PDX tumors. Tissues were processed using the Miltenyi Gentle MACS dissociator. The cells were seeded in a 12-well plate coated with Matrigel. Developed organoids are characterized using, immunohistochemistry, single cell RNA sequencing and 10X spatial sequencing Results: We have successfully developed organoids using frozen tissues from West African European American, and African American TNBC breast patients. We have successfully established five (5) PDXs and their corresponding organoid lines. The organoids are passaged after every 7-14 days, with some organoid lines attaining 20 passages. We are in the process of characterizing the developed PDXs and organoids using immunohistochemistry, single cell RNA sequencing and 10X spatial sequencing and compare their different features. Conclusion: This is an ongoing process, and the efforts will help us have a renewable source of tumor for studying how differential gene expression based on ancestry affects aggressiveness of TNBC among AA. We also aim to use the resources to identify tumor biomarkers for treating aggressive TNBC that disproportionately affects women of western sub-Saharan ancestry. Citation Format: Moses Kamita, Batoul Farran, Sylvester Antwi, Forster Amphonsan-Manu, Josephine Nsaful, Patrick K. Akakpo, Jessica Bensenhaver, Kwabena Agbedinu, Michael Nortey, Nelson Affram, Mohammed Sheriff, Cassandra Mills, Alex Mremi, Theresia Mwakyembe, Ijeoma Aja, Moses Dokurugu, Haythem Ali, Eleanor Walker, Evelyn Jiagge. Characterization of triple negative breast cancer organoids from diverse ethnic populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3990.