Abstract P3-08-03: Establishment of patient-derived xenograft tumor models from breast cancer patients for quantitative elemental profiles and testing candidate therapies

Abstract

Abstract Breast cancer (BC) is a heterogeneous disease comprising different clinical, histopathological, and molecular subtypes. Triple negative breast cancer (TNBC) is among the most aggressive clinical manifestations of breast cancer (BC), and represents a significant clinical challenge to the effective treatment of early metastatic and treatment-refractory disease because of its poor outcomes. Therefore, there exists a need to develop pre-clinical models that retain the characteristics of the original TNBC tumor—e.g., PDX tumor models—to better understand the mechanisms of drug resistance in metastatic TNBC and to effectively evaluate the effects of anti-cancer drugs on patients with this disease. Furthermore, quantitative changes in cellular element signatures, which indicate levels of enzymatic activity, are emerging new biomarkers for cancer in the clinic, but are of yet systematically understudied in tumor samples from breast cancer patients or/and PDX models of these tumors. Due to limitations in current cellular element signature quantitation profiles, there also exists a need to investigate further. Seven samples of advanced BC patient pleural effusion were obtained from Northwestern Memorial Hospital to establish a PDX tumor model in immunodeficient NSG female mice using breast fat pad xenografting and to develop derived 3D spheroid cultures for anti-cancer drug evaluation. To authenticate, STR profiling against with original patient tumor DNA was conducted. Five developed BC PDX tumor models were shown by pathology to have highly heterogeneous characteristics and the metastatic features of the origin patient tumor. Liver and lung metastases were observed in breast fat pad xenografted PDX tumor mice. 3D tumor spheroid cultures were successfully established from original BC pleural effusion or/and PDX tumor cultures. Using the newly developed, highly sensitive, and reliable Wash-Free Inductively Coupled Plasma Mass Spectrometry (WF ICP-MS) method, we evaluated the inorganic phenotypes from samples of breast cancer patient tumor tissue and of the established PDX tumor to quantify the mobile elements (Na, K, and Ca) and less mobile elements (P, Mg, Mn, Fe, Cu, and Zn) simultaneously within the same sample. The data was collected for further analysis of breast cancer inorganic signatures from normal and tumor cells. Our results suggested that BC 3D spheroid cultures and PDX tumor models could serve as models to further study the mechanisms of MBC and serve as promising tools for in vivo and in vitro quick testing and mechanistic studies of novel antitumor drugs respectively. Identifying quantitative elemental profiles is fundamental to understanding the pathologies of various metal-related cancers and thus opens up new opportunities for disease management and therapeutic intervention Citation Format: Wenan Qiang, Haimei Chen, Yi Yang, Andrew Crawford, Demirkan B. Gursel, Jian-Jun Wei, Thomas O’Halloran, Massimo Cristofanilli. Establishment of patient-derived xenograft tumor models from breast cancer patients for quantitative elemental profiles and testing candidate therapies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-08-03.