Project

There are no effective drugs so far to prevent or treat all forms of breast cancer. Yet, according to the WHO, 2.3 million women are affected every year. It is estimated that 685,000 women died from breast cancer in 2020. In addition to the traumas of mastectomy, breast cancer brings the anxiety of metastization.

Brain metastasis in particular are among the most feared complications of breast cancer. Not only the brain is a very sensitive and impactful organ, it also is especially difficult to treat. The psychological and social burden and economic costs of breast cancer are immense. Thus, drugs against the most aggressive forms of breast cancer, including triple-negative breast cancer (TNBC) and their metastasis are urgently needed.

Nonetheless, their development is challenging as it requires the convergence of 3 key elements:

i) a specific therapeutic molecule able to target cells in the tumor microenvironments, both breast and brain, ii) a transporter able to carry this molecule across the BBB reaching metastases in the brain, and iii) reliable animal models in which the anticancer-transporter conjugate can be tested.

In BREAST-BRAIN-N-BBB we will tackle these challenges by means of a minibody specific for subpopulation of cells within TNBC, a peptide able to cross the BBB carrying protein cargoes, and an animal model optimized for TNBC brain metastases. This multi-pronged approach is feasible because of the substantial expertise of BREAST-BRAIN-N-BBB collaborators in their specialty areas and in their proven record of collaboration.

The group of Prof. Miguel Castanho (iMM) has recently discovered peptides from viral protein domains that possess anticancer activity and efficiently traverse the BBB and the group of Prof. João Gonçalves (iMED) has developed minibodies for different targets. These findings add value to BREAST-BRAIN-N-BBB in that they can be judiciously articulated to deliver robust drug leads, selected to maximize “druggability” and eventual pharma transfer. The Project Leader (Prof. Miguel Castanho, iMM) and all Principal Investigators (Dr. Jordi Llop, CICbiomaGUNE; Prof João Gonçalves, iMed; Dr Charles Lawrie, Biodonostia Health Research Institute) in the consortium have experience in transferring technology and negotiating patents with industry.

.