We are developing efforts in several fronts:
-The growing importance of the immune system in the brain when affected by metastasis and the need to combine brain tropic cell lines with genetically engineered mouse models (GEMM), have motivated us to develop several mouse cancer cells with the ability to target the brain from different primary tumors.
-Although currently available brain tropic cell lines are a very useful resource, they only recapitulate partially the genomic complexity of human brain metastasis. Thus, we are establishing patient derived xenografts (PDX) from fresh neurosurgeries that we are incorporating in our current research projects. In addition, CRISPR-Cas9 strategies are allowing us to incorporate human-derived genomic alterations to build more sophisticated models.
-In many cases patients with brain metastasis are heavily treated with systemic or local therapies. We are incorporating such therapies on our models to study the biology of therapeutic benefit and failures.
-The ultimate goal is preventing the development of brain metastasis. However, the majority of existing models do not recapitulate the metastatic process entirely and thus makes complicated to address this goal. We are characterizing in mice primary tumors that in patients are known to have high risk to spread to the brain, in order to establish spontaneous models of brain metastasis.