The human tumour micro-environment modelled in in vitro biomatrices and applied to cancer drug discovery

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New anti-cancer drugs are being developed to target the interactions between malignant cells and normal human cells, such as fibroblasts, that are recruited to support the tumour. Human tumour cells can be grown in rodents but are supported by rodent fibroblasts. The cross-talk between human and rodent cells may not be optimal to evaluate new drugs, limiting the relevance of using xenograft models for such drug screening. We plan to model this environment in vitro, initially using cells derived from patient specimens grown within a matrix to act as a support. The tumour type we will focus on is colorectal cancer in which cells spread to the liver. Growth factors produced by liver fibroblasts are known to support the growth of these invading colorectal tumour cells and we will investigate whether this pathway is functional in our systems as a proof of concept. The cell interactions observed in the biomatrix system will be compared to those present in freshly isolated liver metastases from patients with colorectal cancer. We will also investigate the possibility of using more readily available human fibroblast-like cells to broaden the applications of the technology to different types of cancer and apply reporter systems which are currently being developed by our group to allow real-time monitoring of cell growth and environmental signals without having to harvest the cells.Once validated the findings/protocols will be published and, through the applicants? extensive collaborative links with the pharmaceutical industry, will be disseminated to spread good practice and maximise their uptake and use, overall resulting in reduced inappropriate use of animal models.