A. Identify candidate genes responsible for melanoma brain metastasis.

We injected the melanoma cells into the blood stream of nod/scid mice, and followed tumor development by BLI. Transcriptome profiling with RNA-sequencing was performed on triplicate tumor samples from brain, bone, adrenals and ovaries, using next-generation sequencing on the Illumina HiSeq 2000 platform with paired-end 100-bp sequencing runs (at BGI@UC Davis, Sacramento, CA). This analysis has given us a robust gene profile of 54 overexpressed and 54 underexpressed genes unique for brain metastases, as compared to the genetic tumor profiles from the other organs.
We are currently performing a bioinformatics analysis, comparing our brain metastasis gene profile with gene profiles found in "The Connectivity Map" (from Broad Institute, MA), which is an online database displaying gene profiles of several cancer cell lines after treatment with thousands of common therapeutic compounds. We found that 18 of these compounds, not previously used for cancer treatment, induced similar gene profiles in the cancer cell lines as found in our brain metastasis model. We are currently screening these 18 drugs in vitro for treatment effect in our model.
Based on the in vitro screening, the most promising drugs will be used to study treatment effects in vivo by PET and MRI, according to standardized imaging protocols (6-8). The final aim is to establish a new patient treatment strategy, based on one or a few commercially available drugs not previously described in cancer treatment.