Targeting established brain metastasis

We want to understand what are the molecular mechanisms required to maintain a continued growth once a metastatic lesion has reached a significant size.

The lack of new options for treating brain metastasis and the long-term inefficiency of local therapies, suggest that our knowledge of the biology of brain metastases is poor and unable to translate in innovative therapeutic opportunities. Although there have been genomic and proteomic screens to identify regulatory molecules of brain metastases in humans, the lack of functional validation of these findings prevents understanding the relative contribution to the biology of the disease. In addition, laboratory studies have mainly identified molecular mediators of early stages of colonization that have not been specifically validated at later stages of brain metastasis. Thus, although this stage of disease is the most important clinically, it remains completely unexplored experimentally. The structural differences between early and late stages of the disease (for example, the limited interaction with the microenvironment) along with existing differences between clinical and experimental molecular mediators of the process make us developing a project focused specifically in the advanced stages of the disease. Our goal is to identify signaling pathways necessary for the maintenance of these lesions in the brain. By using advanced molecular technologies including the use of conditional models of the disease, the laboratory analyzes the effects of genetic and pharmacological blockade of these signaling pathways in advanced stages of brain metastases.