Project 1 : The blood-brain barrier and the breast cancer brain metastases
Breast cancer represents the most common cancer among woman. During the cancerisation process, the first stage corresponds to the carcinoma in situ where the tumor cells are located in the breast. However, during the metastatic stage, the cancer cells has developped a secondary tumor distant to the primary site. Breast cancer brain metastases are usually diagnosed several years after the surgical resection of the primary tumor. During this period of remission the cancer cells have acquired specific properties which enable them to target and invade a specific organ. For brain metastases, the breast cacncer cells are able to interact and cross the endothelial cells (ECs) of the blood-brain barrier (BBB) to reach the brain parenchyma. The crossing of the BBB is a pre-requisite of the metastastic colonisation of the brain parenchyma by the cancer cells.
The aim of this project is to understand the interactions developped between the cancer cells and the BBB ECs in order to identify the mechanisms responsible for the crossing of the BBB. The cellular and molecular mediators identify as beeing involved in these early events represent potential targets for the development of novel therapeutic approaches aiming at blocking the initial steps of interactions before the access of the cancer cells to the brain parenchyma.
Project 2 : Blood-brain barrier and pediatric glioma : studying the therapeutic resistance.
Brain tumors are the most frequent solid tumor among children. The DIPG (Diffuse Intrinsic pontine glioma) represents a highly aggressive brain tumor. Despite a lot of progresses during the last decade in the understanding and the treatment of pediatric brain tumors, DIPG represents still a challenge to treat for the oncopediatrician. Once reason can be the reduction of the efficiency of the chemotherapeutic treatments due to the blood-brain barrier. In many pathological conditions, such as brain tumors the BBB are known to have modified properties. However no specific mechanisms has been identified. Hence, it is essential to understand to which extent the BBB properties are influence by the tumor microenvironnement and how it modifies the access of chemotherapeutic drugs to the tumor cells.
The aim of the project is to model the DIPG environnement and study the impact on BBB properties and the consequences on chemotherapeutic drugs transport accross the BBB.
Our approach is based on an in vitro approach using a human BBB model which allows us to identify mechanisms specific to Human. This new and original model will allow to better transpose the results to the clinic. Only a better understanding of the pathological mechanisms involved will help to improve the therapeutic approach specific to DIPG.
