The aim of the laboratory is to understand the molecular pathology of breast cancers, especially triple-negative breast cancers, to identify and validate therapeutic targets.
Breast cancers are the leading cancers in women with about 50,000 new cases per year in France. Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. The efficacy of their therapeutic management has improved considerably in recent years. However, the subgroup of patients with “triple-negative” breast cancer (TNBC), due to the absence of expression of estrogen and progesterone receptors and Her2 overexpression, maintains a poor prognosis. Indeed, they respond well to current therapeutic strategies based on conventional chemotherapies, but they still represent a large proportion of breast cancer deaths, because of a high recurrence rate of residual resistant tumor cells. Alternative treatments are therefore needed to bypass resistance to chemotherapies and to improve the survival rate of TNBC patients.
Our goal is to identify and validate drug targets to offer new ways to treat TNBC. To achieve this aim, we have analyzed a cohort of 200 samples including biopsies of the different breast cancer subgroups, healthy breast tissues and TNBC cell lines. The collected data (DNA, RNA, microRNA, protein) have been analyzed in collaboration with the Bioinformatics (Unit U900) of Institut Curie, in order to provide us with lists of candidate therapeutic targets.
Our team has focused on several of these targets for further validation studies, particularly kinases such as PI3K/AKT, TTK and PLK1 (see Figure 1), as well as TIPIN, a protein involved in DNA replication. Recently, our results led to a phase I clinical trial with a TTK inhibitor. The team is currently analysing the protein arginine methyltransferases and the Wnt signalling pathway in TNBC.