Treatment naive patient-derived xenograft model compared to the post-neoadjuvant model from the same patient diagnosed with triple negative breast cancer
Triple negative breast cancer (TNBC) is an aggressive and difficult-to-treat subtype of breast cancer that typically exhibits rapid growth rates, high rates of metastasis, and resistance to commonly used oncological drugs. Patient derived xenografts (PDX) models have evolved as the new standard that offers a translational approach to the research and subsequent treatment of breast cancer. Here, two novel PDX models for TNBC are characterized: TU-BcX-4QA and TU-BcX- 4QAN. The former derived from a biopsy specimen prior to any therapies, and the latter derived from a mastectomy of the same patient after chemotherapy. In establishing a treatment naÃ¯ve and post-neoadjuvant therapy PDX model pair, a prime model is created that examines the effects of chemotherapy on tumor heterogeneity, clonal selection, and the overall characteristics of a tumor, demonstrating chemotherapyâ€™s ability to fundamentally alter the primary tumor to become resistant to further therapies. Through serial implantation in murine models for tissue propagation, it was observed that TU-BcX-4QAN consistently had a higher tumor growth rate and a smaller number of metastatic lesions that developed in comparison to the TU-BcX-4QA model. In treating the tumor derived cell lines with FDA-approved oncological drugs, variations were distinguished in their responses to commonly used therapies, and it was determined that TU-BcX-4QAN exhibited a more resistant profile. Using qRT-PCR and IHC, further differences between the two models in their contrasting gene and protein expression were discovered. This suggests that treatment can select for certain cancer cells within the primary tumor that allows for the growth of a different tumor altogether and illustrates both the advantages and limitations of the TU-BcX-4QA and TU-BcX-4QAN model pair in translational research.