Brain metastasis is a complication occurring in one third of all cancer patients. The most common cancers giving rise to brain metastases are lung cancer, breast cancer, skin cancer (melanoma) and cancers from the gastrointestinal tract. The prognosis is poor. Treatment strategies available today show minimal effects, as current chemotherapeutic agents are ineffective. The Brain Metastasis Research Group at the KG Jebsen Brain Tumour Research Centre focuses on determining molecular mechanisms which drives metastasis to the brain, in order to find new therapeutic strategies.
New animal models for brain metastasis
We have developed novel model systems where tumour cells from human brain metastases are injected into the blood stream of immunodeficient mice, and the cells metastasize to the mouse brain. This animal model recapitulates most steps of the metastatic cascade, and a better understanding of the molecular mechanisms behind tumor metastasis may thus be obtained.
Development of novel animal models. A. Systemic metastatic disease, demonstrated by bioluminescence imaging weeks 1, 3 and 5 after cell administration in four mice (supine and prone view). B. i. T1w MRI showing multiple brain metastases after 5 weeks (scale bar 2mm). ii. H&E staining of tumors seen in i. (scale bar 1mm). The melanocytic phenotype of the brain tumors was confirmed by immunohistological staining for iii. S-100 protein and iv. MITF. C. Single melanoma cells visualised by T2*w MRI (top right). Histology demonstrates single iron oxide labelled cells, and thus confirms that hypo-intensive spots seen on MRI in fact are single tumor cells.
Ongoing research activities
We are using advanced preclinical imaging – magnetic resonance imaging (MRI), positron emission tomography (PET) and bioluminescence imaging (BLI) – to show that metastatic tumour development in the animal models are very similar to what is seen in the clinic. More information on the imaging modalities can be found here.
We are currently expanding on the imaging technology, by implementing novel theranostic nanoprobes to deliver therapeutics directly to the animal brain metastases. Also, we are trying to increase drug delivery to these metastases, by using new compounds which are able to open the blood brain barrier. In an ongoing project where we have performed gene expression analysis on animal brain metastases, we have found several compounds that may have significant therapeutic effects in the clinic.