We have generated a collection of patient-derived tumour xenografts (PDTXs) aiming at having a representation of the breast cancer subtypes. All of these PDTXs are being extensively characterized with whole genome/whole exome sequencing, expression profiling, miRNA profiling and whole genome/reduced-representation bisulfite sequencing.
Importantly for all the models generated we have matched normal DNA, and the originating primary tumour or metastasis where a similar molecular profiling is performed. We have now optimised protocols to derive viable single-cell suspensions from each xenograft, which we designate as patient-derived tumour cells (PDTCs). These PDTCs can be used 24 hours after collection for in vitro perturbation (TGFβ exposure, miRNA over-expression, shRNA or RNAi), but crucially also for high-throughput ex vivo drug screening.
In collaboration with the Sanger Institute we have now conducted pilot experiments screening around 100 compounds in 17 distinct PDTCs, establishing proof of principle. Our aim is to correlate the drug responses/resistance with the molecular profiles of the PDTCs/PDTXs and hence identify novel predictive biomarkers for translational use.
We have made publicly available our data on https://caldaslab.cruk.cam.ac.uk/bcape/ following our publication (Bruna et al., Cell 167, 260 - 274 (2016) ).
The Breast Cancer PDTX Encyclopaedia (BCaPE) provides tools for visualizing, querying and downloading data from a large collection of highly molecularly annotated breast cancer patient-derived tumour xenografts (PDTX). The biobank was developed by Carlos Caldas' laboratory at the Cancer Research UK Cambridge Institute and represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies, including identification of biomarkers of response or resistance.