Building biology in 3D for cancer drug discovery and precision medicine by decoding patient derived scaffolds (PDS)

Patient-derived scaffolds and analyses of adapting cancer cell lines can monitor malignant properties of a cell-free cancer microenvironment highlighting distinct links between scaffold influences and clinical aggressiveness in cancer. The protein composition of the cell-free cancer microenvironments influencing adapting cancer cells have been defined by quantitative mass spectrometry and results indicate clear clustering of PDS differing in extracellular matrix related proteins as well as immunoregulatory and metabolic regulators. Interestingly both the defined clusters as well as individual imprinted proteins in the cell-free scaffolds are linked to clinical behaviours of the cancer and data from breast cancer and colorectal cancer will be presented. The multitude of proteins imprinted in the cell-free cancer scaffolds representing various tumour biological activities and cell types, supports the importance of the cancer microenvironment in influencing varying disease behaviours. The in vivo identified proteins can be used for improved disease subtyping, cancer drug targeting and importantly to construct optimal synthetic 3D-models that can be used for human-like drug discovery and validation of novel cancer treatments. Data from the first prototypes of human-mimicking synthetic scaffolds will be presented and discussed in relation to other 3D-based growth models available for cancer discovery.