Finding new uses for old drugs in clinical treatment of brain metastases
We are focusing on elucidating how combination of multiple cancer gene signatures are responsible for malignant disbursement of cancer cells from the primary site to the brain.
To study such complex processes, we have developed novel animal models to study metastasis to the brain, in particular related to human melanoma and lung adenocarcinomas. We have developed animal models where these cancers mainly metastasize to the brain and to a lesser extent to other organs. From the brain metastatic lesions, we have identified by deep sequencing technology, candidate gene lists that reflect a brain metastatic signature. Based on this list, we have identified key compounds, already in use on patients for other conditions, which may reduce brain metastasis. Our aim is to bring the lead compound into clinical trials.
Treatment of animal brain metastases. The number of brain metastases as well as total tumour volume decreased dramatically after daily drug treatment for 10 weeks. Animal survival also increased significantly, and 3 of the treated animals were still alive and healthy at the end of the study.
We are currently screening the drugs in vitro and in vivo, and preliminary data show that we are able to inhibit tumour development both in cell culture and in animals. Based on these encouraging results we will aim for bringing one of these compounds into a clinical Phase I trial during the coming 4 year period.