Establishment of two Breast Cancer Patient Derived Xenograft (PDX) lines and their respective treatment-resistant PDX variant

Sebastián Real¹, Sofía Masuelli¹, Paula Valdemoros², Gisela Berra³, Romina Seeling³, María Roqué¹


Patient Derived Xenografts (PDX) are widely used in basic, translational and clinical research of cancer mainly because they conserve the original histopathology and chemo-sensitivity of the donor tumor, and they are stable across subsequent passages. In Argentina this tool is not extensively available, and most cancer research labs use cell culture for in vitro experiments. Here we present the establishment of two lines of breast cancer PDXs, both generated in Mendoza from donor patients of local public and private hospitals. The first PDX (called M1), lacks the expression of HER2, ER and PR, (triple negative), and shows a very high growth rate, needed to be passed every 3 weeks. In line with its aggressive phenotype, M1 PDX is not responding optimally to classical chemotherapy. The second PDX, (called H1), presents overexpression of HER2 receptor and lacks ER/PR. Unlike M1, H1 PDX has an intermediate growth kinetics, being passed every 2,5 months, and responds suitably to HER2- targeted therapy Trastuzumab (TZM). With the purpose of developing an animal model to study the mechanism of TZM resistance, we generated a variant of H1 that remains unresponsive to TZM, by treating the mice with increasing doses of TZM in every successive passage (15-20-25mg/kg). The H1-TZM-resistant PDX does not respond to TZM at almost twice of the initial doses. We believe that the generation of this tool will potentiate the clinical and translational research not only in our group but in all the breast BC research groups in Argentina.