A new combination therapy to inhibit the growth of 50% of triple-negative breast cancers
Dr. Nor Eddine Sounni's team at GIGA-Cancer and Prof. Dr. Guy Jerusalem have discovered a new therapeutic combination to inhibit the growth of half of triple-negative breast cancers (TNBC).
Triple-negative breast cancer (TNBC) is so called because it does not have the three common markers of breast cancer: the estrogen receptor (ER), the progesterone receptor (PR) and the HER2 protein. Not like breast cancers with these markers, there is no approved targeted therapy for TNBC. One of the main challenges of cancer research related to TNBC is the complex molecular heterogeneity of TNBC tumors and their aggressive pattern with high rate of recurrence.
Researchers conducted at GIGA-Cancer have helped to stratify these TNBC tumors by using a tumor biobank available at the University Hospital at Liège University (CHU) and a biobank of patient derived xenograft (PDX) in collaboration with researchers from the Marie Curie Institute in Paris. Based on their previous study that revealed a new signaling pathway involving EGFR, MT4-MMP and RB in TNBC cell lines (Paye et al., 2014, Cancer Research), they determined a new subtype of TNBC that expresses these three biomarkers (EGFR, MT4-MMP and RB). They found that 50% of triple-negative breast cases have the three biomarkers and therefore they suggested that these cancers could be treated with the available targeted therapies against EGFR and against an RB regulator called CDK4/6.
By using PDX mice that express or not all three biomarkers, they demonstrated that a combonation of two drugs, erlotinib and palbociclib, respectively targeting EGFR and the RB inhibitor CDK4/6 eradicated the growth of these tumors. In contrast, PDX mice that do not have the three biomarkers together remain insensitive to treatment.
This work, which constitutes the thesis subject of the PhD student Pierre Foidart is published in Clinical Cancer Research and opens up new therapeutic perspectives for patients selected on the basis of the presence of these three biomarkers.
Expression of MT4-MMP, EGFR and RB in triple negative breast cancer strongly sensitizes tumors to erlotinib and palbociclib combination therapy Pierre Foidart, Cassandre Yip, Jean Radermacher, Mehdi Lienard, Silvia Blacher, Laetitia Montero-Ruiz, Erik Maquoi, Elodie Montaudon, Sophie Chateau-Joubert, Joelle Collignon, Michel Coibion, Véronique Jossa, Elisabetta Marangoni, Agnes Noel, Nor Eddine Sounni* and Guy Jerusalem*. *Co-senior authors. Clinical Cancer Research, 2018.
Published OnlineFirst November 30, 2018 doi: 10.1158/1078-0432.CCR-18-1880
Image showing two triple negative breast cancer (TNBC) tumors. On the left a tumor negative for the RB protein and on the right an RB positive tumor. The TNBC tumor on the right is sensitive to the therapeutic combination of erlotinib and palbociclib, while the tumor on the left is insensitive to this treatment
