Patient-derived scaffolds - a model for identifying cancer promoting properties of the tumor microenvironment relevant for cancer drug design and treatment prediction

Abstract: Despite of the huge progress in cancer precision medicine there is an urgent need for more efficient cancer therapies and treatment predictive tools for identifying the patients that will benefit of the various treatment strategies. Biological cancer heterogeneity on multiple levels, including the tumor microenvironment, is contributing to the complexity of the disease and difficulties reliable treatments and the cancer cure. We have focused on decoding the intricate cancer microenvironment harbouring several relevant cell types as endothelial cells, fibroblasts and immune cells as well extracellular matrix (ECM) and several imprinted components as peptides and metabolites. The interplay between cancer cells and cancer progressing and limiting components in the microenvironment plays an important role for the disease behaviour and seems to influence key clinical factors as disease recurrences and metastasis as well as cancer drug resistance. The innovative aspect of the presented human-based model is that this novel diagnostic and research platform can decode patient cancer samples by generating culture systems where patient-specific cancer microenvironment information is retained. Extensive studies have shown that decellularized patient-derived scaffolds (PDSs) exhibit heterogeneity in structure and composition related with clinical properties indicating that the PDS can reveal highly relevant information about the malignancy grade of the cancer microenvironment for a patient. By combining the scaffold platform with existing cancer treatments, we have also shown that cancer cells cultured in PDSs modified their response to chemotherapy agents and endocrine therapies supporting the future potential of this platform to evaluate tumor drug response in cancer patients. Besides, by large scale mass spectrometry analyses of the cell-free PDSs from colorectal and breast cancer samples we have observed that many of the detected proteins were related to immune response. PDS cultures of different cancer cell lines also influenced the expression of relevant immunotargets as well as the behaviour of cancer and immune cells added to complex PDS co-culture systems. The data support that the PDS can reveal unique information about various key processes in cancer progression including immune modulating properties of specific cancer microenvironments essential for the development of more efficient and personalized cancer therapies.