Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. The treatments for this disease are improving patients’ life expectancy. Unfortunately, the increase of free-disease survival also comes with a higher probability for suffering from the dissemination of the cancer cells to distant organs (metastasis). Amongst all the potential sites that circulating tumour cells may colonise, the central nervous system has the worst prognosis: 1 month without treatment or ca. 14 months even after the most advanced therapies.
Harnessing the body's immune response to tumours (immunotherapy) has recently shown promise for the treatment of primary cancers outside the brain. Together with surgery, radiation and chemotherapy, it has become the fourth pillar for the treatment of a broad panel of cancer types. Although this strategy has gained great momentum in the clinic, only a few studies have tested its validity for breast cancer brain metastasis.
The neuroinflammatory scenario driven by the immune system during the brain colonisation of tumour cells is a hallmark. One key molecule in the immunogenic response within the brain is β-galactoside-specific animal lectin galectin-3 (Gal-3). Galectin-3 is a promiscuous protein of the lectin family expressed both in cancer cells and a variety of immune system cell types (microglia included), constitutively or in response to different kinds of insults. In other diseases within the central nervous system, microglial Galectin-3 has shown a negative effect on disease progression (e.g. Alzheimer’s and Parkinson’s’ disease) turning microglia into a harmful phenotype. Since microglial cells are the resident macrophages in the brain, it is of vital importance to study the role that this protein may exert on microglial activation during brain metastasis progression.
This project seeks to find new strategies to shift the microglial response into an anti-metastatic state, and thus, improve survival in breast cancer brain metastasis (BCBM) patients, an urgent and unmet clinical need. Our approach will use a balanced combination of established and novel in vitro and in vivo brain metastasis models, in which anti-tumourigenic therapies that have not previously been considered in a BCBM context will be tested.
