Improving drug delivery in gliomas

Drug delivery into the brain is regulated by the blood–brain interfaces, including the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). These selective barriers present a high impermeability to most substances, with the selective transport of nutrients and transporters preventing the entry and accumulation of possibly toxic molecules, comprising many therapeutic drugs.

Transporters of the ATP-binding cassette (ABC) superfamily have an important role in drug delivery, because they extrude a broad molecular diversity of xenobiotics, including several anticancer drugs, preventing their entry into the brain. Gliomas are the most common primary tumors diagnosed in adults, which are often characterized by a poor prognosis, notably in the case of high-grade gliomas. Therapeutic treatments frequently fail due to the difficulty of delivering drugs through the brain barriers, adding to diverse mechanisms developed by the cancer, including the overexpression or expression de novo of ABC transporters in tumoral cells and/or in the endothelial cells forming the blood–brain tumor barrier (BBTB). In this project, we will explore the impact of glioma pathology on the signalling pathways regulating ABC transporters, and also other transporters that can be a target to improving drug delivery.