A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds

Area of Science:

• Oncology
• Genomics
• Translational Medicine

Background:

• Breast cancer exhibits significant inter- and intra-tumor heterogeneity, posing challenges for effective pre-clinical modeling.
• Accurate pre-clinical models are crucial for understanding tumor evolution and developing targeted therapies.

Purpose of the Study:

• To establish and optimize a platform for maintaining breast cancer patient-derived tumor xenografts (PDTXs) and their derived tumor cells (PDTCs).
• To assess the preservation of intra-tumor genomic clonal architecture in these models during serial passaging.
• To evaluate the utility of these models for high-throughput drug response assessment and biomarker discovery.

Main Methods:

• Generation of a large collection of breast cancer PDTXs.
• Optimization of an integrated platform for in vivo maintenance of PDTXs and short-term culture of PDTCs.
• Assessment of genomic clonal architecture preservation through serial passaging.
• High-throughput drug response screening in PDTCs and validation of ex vivo responses in vivo.

Main Results:

• The established platform successfully maintained morphological and molecular characteristics of originating tumors.
• Intra-tumor genomic clonal architecture was largely preserved in both xenografts and short-term PDTC cultures.
• High-throughput drug screening in PDTCs showed predictive value for in vivo responses, identifying potential biomarkers.

Conclusions:

• The developed biobank of PDTXs and PDTCs accurately captures breast cancer heterogeneity.
• This resource is valuable for pre-clinical pharmacogenomic studies, including biomarker identification for treatment response and resistance.
• The platform facilitates efficient drug screening and validation for personalized breast cancer therapy.