The study of spontaneous breast cancer metastasis in vivo with patient-derived material generally fails to reproduce the metastatic behavior observed in patients, whereas the major metastatic site is the bone, which is indeed the target organ selected to be featured in the B2B device.
A recent study from our partners at Prof. Nicola Aceto’s lab (now at ETH Zurich) provides evidence that when using metastasis-derived Circulating Tumor Cells (CTCs) rather than primary tumor cells as the source of transplanted cells in the in vitro / in vivo models, the consequent metastatic profile mirror the disease status of the original patient at the moment of CTC isolation.
This method can be completed with CRISPR-based genetic screens for unbiased identification of disease-relevant genes, including specific genetic dependencies for each step of the metastatic process in vivo. For example, the results of this approach allowed us to pinpoint previously unappreciated genes whose expression regulates CTC cluster formation, as well as genes that regulate the intravasation of both single and clustered CTCs and organ-specific metastasis.
Therefore, this novel CTC-based tool helps to study spontaneous breast cancer metastasis in a highly clinically relevant fashion. This model, in combination with a CRISPR-based approach, represents a new tool to reclassify driver genes involved in the spread of human cancer, providing insights into the biology of metastasis and paving the way to test targeted treatment approaches.