Patient derived xenograft (PDX) models are established by implanting tumor tissue from patients into mice, and are a valuable tool to investigate drug response. We have established 9 patient derived xenograft (PDX) models from patients with peritoneal metastasis from colorectal cancer and pseudomyxoma peritonei.
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A challenge with drugs given intraperitoneally is the short exposure time achieved with cytotoxic drugs as they are rapidly absorbed from the peritoneal cavity. It is therefore a need for therapeutic approaches that enable high drug concentrations combined with prolonged residence time of chemotherapeutics in the peritoneal cavity to improve the anti-tumor activity.
A common treatment for patients with peritoneal metastasis is cytoreductive surgery to remove all visible tumor followed by circulation of hyperthermic chemotherapy in the abdominal cavity for 90 minutes to kill the small remaining tumors. The rationale behind this procedure is that the heated chemotherapy can increase the penetration of drug into the tumor, activate the immune system and thereby improving the response to treatment. HIPEC is a complicated procedure with many important parameters, such as choice of drug, treatment duration and temperature of the chemotherapy, but there is no standardized method of performing HIPEC and there are therefore large variations between treatment centers.
Patient-derived tumor organoids are generated by tumor tissue removed from patients being further grown in the laboratory, in the form of 3D structures in a gel-based growth medium. This allows the cells to develop more naturally than when grown in conventional 2D models. Compared to animal models, organoids are less complex, but more efficient in terms of time and costs. Organoids can therefore be established for several individual patients, which can hopefully lead to patient-specific treatment.