Programme EpiRT sur les tumeurs rhabdoïdes


Combination of epidrugs in Rhabdoid tumors : a comprehensive analysis of effectiveness and of the mechanisms of resistance

This program is co-funded by the Enfants sans Cancer 2020 race and was selected following the Fight Kids Cancer call for projects that we launched in January 2020. Learn more


About Rhabdoid Tumors in Children

Rhabdoid tumors are rare but highly aggressive cancers that mainly affect young infants and children under 3 years old. This cancer can develop in multiple organs, including the brain, and treatment usually involves a combination of surgery, radiotherapy, and chemotherapy. This therapeutic approach is effective for only a minority of patients, who often suffer from significant long-term effects. Therefore, it is necessary to develop effective treatments targeting the specific molecular and genetic characteristics of these tumors.

Recent research has shown that 95% of rhabdoid tumors are associated with an alteration of the SMARCB1 gene, which is supposed to prevent cell proliferation. This genetic mutation can be hereditary (germline mutation) or occur only in tumor cells, as is often the case.


About EpiRT

SMARCB1 regulates the expression of many genes within the cell. By affecting DNA remodeling (compaction or decompaction), certain genes become accessible or inaccessible, thus facilitating or inhibiting their expression. This is known as epigenetics, which involves regulatory mechanisms of gene activity in a cell that can be passed on to its daughter cells during cell division. These changes are associated with many diseases, including cancer. Abnormal epigenetic regulations can lead to the production of proteins that enhance the proliferation of cancer cells or limit the expression of factors that prevent cell division.

These discoveries are relatively recent in biology, and we are increasingly witnessing the emergence of epigenetic therapies in healthcare. This project aims to develop “epidrugs” that target the altered function of SMARCB1, such as EZH2 or DNMT inhibitors, which have shown promising but temporary efficacy signals in rhabdoid tumors. These inhibitors have been tested in combination with other treatments on rhabdoid tumor models in the laboratory.


Project Progress

Among the tested molecules, the combination of 2 agents (names remain confidential) has shown significant effects in blocking tumor progression of human tumors in a mouse model. Additional studies will be conducted soon, including the genetic profile evolution of treated tumors to better understand this therapeutic mechanism, which has potential for clinical development. Researchers will also analyze the impact of these treatments on the tumor microenvironment, particularly whether the immune system becomes more active against these tumors.


EpiRT Project Summary

  • Coordinating Investigators: Drs. Franck Bourdeaut, Kornelius Kerl, and Céline Vallot
  • Program Duration: January 2021 – January 2025
  • Countries Involved: France, Germany
  • Funding: Fight Kids Cancer: €500,000, including funding from Imagine for Margo: €239,448


Découvrez les autres essais que nous co-finançons pour accélérer la recherche contre le cancer des enfants.