Abstract B121: Developing organoid model to study drug-resistant breast cancer cells

Abstract Breast cancer (BCa) is one of the most common forms of cancer worldwide and one of the leading causes of mortality for women in America. Drug resistance is one of the major causes of treatment failure and the leading contributor to the BCa mortality rate. Approaches employed to study the mechanisms of drug resistance development in BCa in the laboratories have been successful with the use of traditional 2D culturing systems. However, this approach does not accurately reflect the 3D interaction of cancer cells with the matrix and microenvironment. This phenomenon has led to the idea that creating 3D organoids from BCa cells to mimic the organs they metastasize to will provide an ideal environment for studying cancer drug resistance in vitro. Hence, we aimed at developing breast cancer drug-resistant cell models for effective anticancer drug discovery studies in the future. We co-cultured parental HCC 1806 triple-negative breast cancer cells alongside their carboplatin- and rhenium-resistant derivatives with Matrigel for up to two weeks, changing media and taking organoid photomicrographs bi-daily. We observed the formation of spheroid structures, which were the cancer organoids, from day 2 of the incubation period. Also, the organoids increased in size with time and became more prominent from Day 6 to 12. Although the organoids were observed to have similar morphological appearances in terms of shape, they vary greatly in size, with rhenium-resistant organoids having the largest organoid size, followed by carboplatin-resistant cell organoids, while HCC1806 parental had the smallest organoid size, displaying the difference in the aggressiveness and tumorigenic natures among the cancer cells studied. In the future, we will start doing drug treatment after organoid formation in preparation to mimic an in vivo microenvironment better and compare organoid formation. Discovering the mechanism of BCa cell interaction with different drugs by researching it in a 3D organoid can grant us a better understanding of how BCa develops drug resistance and what we can do to counteract it. Citation Format: Johnaton A. Tyrell, John A. Obadipe, Santosh Mandal, Dipali Sharma, Valerie A. Odero-Marah. Developing organoid model to study drug-resistant breast cancer cells [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B121.