Abstract A060: Organoid Culture as a Unique Resource for Studying Aggressive Triple Negative Breast Cancer in African American

Abstract

Abstract Introduction Triple negative breast cancer (TNBC) among women with African ancestry has been shown to be more aggressive than in women of European ancestry. However, the root cause for this disparity is not fully understood. In our previous studies, we show that the gene expression in the breast cancer stem cells of TNBC tumors was differential based on Western sub-Saharan ancestry. To study the role of African ancestry in the biology of TNBC, we have developed patient-derived organoids (PDO) from African (Ghanaian) and African American tumors that will be available for research. Organoid culture has the capacity to mimic the physiological tissue organization and functionality and has been used as an invaluable tool for disease modeling and drug discovery. Objective The objective is to develop and characterize PDOs based on African TNBC that will serve as a renewable source of African tumors for breast cancer research. Methods Through our international collaboration called Precision Medicine for Aggressive Breast Cancers (PMABC), we obtained fresh patient tumors from continental Africa (Ghana) and African American tumors from Henry Ford Health. PDOs were developed form both primary tumors and patient-derived xenografts (PDX). Tissues were processed using the Miltenyi Gentle Mac. The cells were seeded in a 12-well plate coated with Matrigel. Developed organoids are characterized using single cell RNA sequencing as well as 10X spatial sequencing Results We have successfully developed organoids using frozen tissues from both West African and African American breast patients. We have successfully established four (4) organoid lines from individual primary breast cancer tissues and one PDX. The organoids are passaged after every 7-14 days, and the highest passage so far is passage number 12 for the organoids from primary tissues and passage number 15 for the PDXs. We are in the process of characterizing the developed organoids using single-cell assay in comparisons to their primary tumor of origin. Conclusion Establishment of organoids has helped us have a renewable source of tumor for studying the aggressive TNBC among Women with African ancestry. We aim to use the organoids to identify tumor biomarkers for treating aggressive TNBC that disproportionately affects women of western sub Saharan ancestry. Citation Format: Moses Kamita, Kurt Fernando, Sylvester Antwi, Forster Amponsah-Manu, Josephine Nsaful, Kafui Akakpo, Jessica Bensenhaver, Kwabena Agbedinu, Michael Nortey, Nelson Affram, Mohammed Sheriff, Cassandra Mills, Alex Mremi, Jieoma Aja, Moses Dokurugu, Haythem Ali, Eleanor Walker, Max Wicha, Evelyn Jiagge. Organoid Culture as a Unique Resource for Studying Aggressive Triple Negative Breast Cancer in African American [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A060.