Researchers at the Laboratory of Preclinical Investigation at the Institut Curie in Paris (France) have been developing animal models of human uveal melanoma and liver metastases as early tools in drug development.
Uveal melanoma (UM) is a rare eye cancer found in 5 individuals per million every year. Although the primary disease in the eye can be treated today, it can spread to the other parts of the body, forming tumours called UM metastases. Half of all UM patients develop metastasis, mainly in the liver, where currently no effective treatment is available.
Cancer models can be developed by implanting human tumour fragments into other animals, under strict ethical controls, as a means of early testing of potential drugs. These models are called patient-derived xenograft (PDX) models, and are now recognised across cancer research as very relevant research tools, as transplanted tumours retain the characteristics of corresponding patient tumours, and reflect other complexities of human cancer. As such, they can help to identify potential drugs before the initiation of expensive clinical trials.
These models have already been successfully used in the past to test new drugs, helping to generate sufficient evidence prior to the initiation of human clinical trials. Under the UM Cure 2020 project funded by the European Union’s Horizon 2020 research and innovation programme, the Institut Curie has been focusing on extending the collection of PDX models for UM liver metastases, in order to develop a panel of PDX models that are more representative of metastatic patients considering the diversity of the disease.
Eighty metastatic human tumour specimens obtained after surgery were transplanted into mouse models, of which thirty PDX models were successfully obtained. These models have been characterized in the laboratory with a particular interest in specific tumour abnormalities in order to identify targets for future drug developments. In parallel, efforts are being made to improve animal models in order to better represent the metastatic form of UM. These methods include targeting specific organs for animal model transplantation (such as the liver), and the development of animal models that show similar immune responses to humans.