iGReD - Molecular Pathophysiology of Adrenal and Endocrine Tissues (MOP@ET)

Published on June 8, 2021 – Updated on October 26, 2021

Through the development of genetically engineered mouse models, our team deciphers the molecular mechanisms resulting in development and progression of adrenocortical carcinoma, a rare cancer of the adrenal gland.

Lung metastasis of ACC from Znrf3 and TP53 double KO mice (stained by GFP in green). It is surrounded by CD45+ immune cells (red) that do not infiltrate metastatic tissue.

Lung metastasis of ACC from Znrf3 and TP53 double KO mice (stained by GFP in green). It is surrounded by CD45+ immune cells (red) that do not infiltrate metastatic tissue.

Adrenocortical cancer (ACC) is a rare but aggressive cancer associated with poor prognosis (5 years survival <30%). In order to improve ACC treatment, our team, which recently received a label from Ligue Nationale Contre le Cancer, is interested in the molecular mechanisms involved in the development and malignant progression of ACC. For this, we have developed genetically engineered mouse models that recapitulate alterations of WNT/ β-catenin and P53 pathways, that are frequently observed in ACC patients. Through analysis of these models, our goal is to answer three major open questions:

  1. What are the mechanisms associated with metastatic progression of ACC?
  2. What is the role of the immune microenvironment in ACC progression?
  3. What is the role of glucocorticoids produced locally by ACC, in the acquisition of an aggressive phenotype?

Our approaches rely on histological and molecular analyses of our models of metastatic ACC, RNAseq, WES, and development of genetic and pharmacological tools, allowing modulation of the recruitment and activation of different immune cells populations. On the long term, we will use these models to evaluate novel therapeutic approaches targeting glucocorticoids and the tumour microenvironment to improve ACC patients’ prognosis. Our projects are developed in collaboration with Dr Marc Bajénoff (CIML, Marseille), Pr Martin Fassnacht (Würzburg, Germany) and Pr Jérôme Bertherat (APHP, Paris).