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IMoST - Genomic, protein and immune biomarkers of triple-negative breast cancer relapse
Tissue morphology and protein quantification by single and multiple IHC, live or after digitization Gene / protein expression ± spatial resolution (GeoMx™ Digital Spatial Profiler (Nanostring) and / or RNA-Seq, either global or targeted) Functional validations on cellular and animal models
"Triple negative" breast cancer tissue stained with double immunohistochemistry. The zone rich in Zeb1+ tumor cells (brown signal) is very poor in CD8+ anti-tumor lymphocytes (purple signal). Ouled-Dhaou M, ... , Radosevic-Robin N, Am J Ca
The main focus of our research is the discovery of biomarkers of relapse for the most aggressive breast cancer, called "triple negative" (TNBC). It has been shown that the metastatic progression of cancers results from a balance between the intrinsic genetic alterations of malignant cells and the extrinsic control of their survival, carried out by the benign cells of the tumor microenvironment. Breast cancers also show significant heterogeneity in histological and biological characteristics, largely reflected by their clinical behavior. TNBC is characterized by a particular development, with an overrepresentation of rapid relapses (<1 year) and rare late relapses (> 5 years). Finally, some tumors never relapse.
However, we still do not have reliable biomarkers that could indicate the onset and / or type of relapse in a patient affected by a TNBC. We are therefore evaluating the expression of genes and proteins in tumor tissue, the cellular and molecular composition of its microenvironment, and the impact of modifications of these compositions on the course of the disease and / or its response to various treatments. In addition to tissue biomarkers, we are interested in molecules released by tumor tissue into the blood as well as characteristics of circulating immune cells, systemic immune status being closely related to metastatic progression.
We operate the following technologies:
- Visual analysis of tissues and cells, under a microscope or using scanned images
- Detection and quantification of proteins by single and multiple chromogenic immunohistochemistry
- Quantification of gene / protein expression with or without spatial resolution (Nanostring technology, nCounter® instruments and GeoMx™ Digital Spatial Profiler)
- Molecular analyzes of RNA or DNA by high throughput sequencing (targeted or not transcriptomes and exomes on Illumina NextSeq)
- In vitro functional analyzes: proliferation, migration, invasion, apoptosis tests on different cell models
- In vivo functional analyzes: subcutaneous and orthotopic xenografts in MRI-nude mice. Analysis of tumor growth and metastatic dissemination.
Other GCCA Partners
- Jean PERRIN Comprehensive Cancer Center – Clinical Research Division
- Jean PERRIN Comprehensive Cancer Center - Pathology Department
- Jean PERRIN Comprehensive Cancer Center - Oncogenetic Department
- Jean PERRIN Comprehensive Cancer Center - Medical Oncology