Abstract P6-04-03: Anticancer potential evaluation of natural products with breast cancer organoids

Abstract

Abstract Background: Breast cancer is one of the most malignant diseases threatening the health of our society. It is estimated that there will be more than 300,000 new cases of breast cancer in the US in 2018. Currently, surgery combined with chemotherapy is the most common strategy for breast cancer treatment. However, due to the cancer heterogeneity induced drug resistance, continuously developing new anti-cancer drugs is of great importance. Nature compounds extracted from traditional Chinese herbs were demonstrated to have anti-cancer activity through cell based experiments, but lacking suitable pre-clinical models, which could faithfully reflect in vivo tumor property, prevents these compounds from further characterizing. Now cancer organoids, as a new in vitro 3-D culture technique, were demonstrated to largely retain the biological characteristics of tumors from patients, and potentially served as an ideal platform for drug sensitivity test. Breast cancer organoids study was relatively limited when comparing with other type of cancer such as colon cancer. In this study, we set up system to efficiently establish breast cancer organoids from clinical patients and further test the sensitivity of these organoids to various nature compounds. Methods: We collected fresh breast cancer tissues from 17 patients after surgery and established organoid models. Different dosage of herb derived nature compounds such as Gypenoside, Berberine, Oxymatdne, Sophoridine, Betaine, Chelerythrine Chloride, Harmine, Cantharidin were used to treat each organoid clone. Luminescent cell viability assay was used to indicate tumor survival rate. Results: Organoid were successfully established for all 17 patients. A Short Tandem Repeat (STR) analysis was employed to detect sample contamination and HE(hematoxylin and eosin) stain was used to confirm the histological features. All organoids were resistant or slightly response to Oxymatdne, Sophoridine, Gypenosides, Betaine. For Berberine and Cantharidin, 10 out of 17 and 14 out of 17 organoids showed dose-dependent inhibition efficacy respectively, and the rest showed resistance. For Chelerythrine Chloride and Harmine, only organoids from specific patient showed sensitivity in a dose-dependent manner. Interestingly, different patients had distinct response pattern to these nature compounds, indicating organoids were useful in the anti-cancer lead screening and biomarker identification. Conclusion:Breast cancer organoid, as a wonderful pre-clinical model largely containing tumor in vivo property, provides an ideal platform for new drug discovery and inhibitor screening. Moreover, serving as in vitro replacements for breast cancer, organoid models make it possible to test drug sensitivity for individual patient to achieve precise and personalize medication. Citation Format: Zhang B, Xu X, Cai H, Sun Z. Anticancer potential evaluation of natural products with breast cancer organoids [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-04-03.