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

REAL SEBASTIAN; ROQUÉ MORENO MARIA

Simposio; BUENOS AIRES BREAST CANCER SYMPOSIUM; 2021

Establishment of two Breast Cancer Patient Derived Xenograft (PDX) lines and generation of the respective treatment-resistant variant.Patient Derived Xenografts (PDX) are widely used in basic, translational and clinical research of cancer mainly because they i. conserve the original histopathology and chemosensitivity of the donor tumor, and ii. they are stable across subsequent passages. In Argentina this tool is not largely used and most cancer research labs use tissue culture for in vivo 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), lacked expression of HER2, ER and PR, (triple negative), and showed a very high growth rate, needed to be passed every 3 weeks. In line with its aggressive phenotype, M1 PDX is not well responding to classic 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 responses good to the 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 doesn’t respond to TZM at almost twice of the initial doses. To our knowledge, we are the firs group in Argentina in generating BC PDXs with their respective treatment resistant variant