Roman Chabanon Discovering new therapeutic approaches to stimulate immunity against certain cancers

Defects in DNA repair pathways and cancer cells

DNA carries our genetic information. Its integrity and stability are essential for our cells to function properly. Throughout our lives, our DNA is exposed to many factors that can damage it. Every cell in our body is constantly triggering mechanisms to repair it in order to protect our genome.

In cancer, the genes that control DNA repair are defective. The cancer cells’ DNA accumulates a large number of mutations that often promote their growth. But defects in DNA repair pathways also make cancer cells vulnerable to certain drugs, such as PARP inhibitors,

which block one of the mechanisms they use to repair their DNA, causing an accumulation of DNA damage that eventually triggers cell death. PARP inhibitors target this mechanism to selectively destroy cancer cells whose DNA repair is already deficient, such as in some lung, breast and ovarian cancers.

PARP inhibitors and immune system stimulation

Roman Chabanon discovered a second, previously unknown and unexplored property of PARP inhibitors: their ability to stimulate the immune system. He has shown that PARP inhibitors can trigger the recruitment of immune cells at the tumor site, thereby prompting the immune system to target it. This plays a key role in the anti-tumor mechanism of PARP inhibitors and opens up new prospects for using these targeted therapies on patients, especially in combination with immunotherapy.

During his post-doctorate, Dr. Chabanon wants to use new functional genomics techniques to deepen his research on therapies targeting DNA repair. His work will help extend the lives of people with aggressive cancers for which immunotherapy alone is sometimes ineffective, as in the case of some lung cancers.

"PARP inhibitors affect tumor cells’ interactions with their immunity microenvironment. This radically changes our view of their cancer-fighting potential." Roman Chabanon