Marie-Uriel Chantraine

Marie-Uriel Chantraine

Interview with Marie Dutreix

Julia Vollerin
07/17/2018
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Could Dbait molecules be the answer to cancer radioresistance? With clinical trials of these radiosensitizers ongoing, Marie Dutreix gives us the lowdown on this innovation.

Dbaits were developed in your laboratory; could you tell us the story behind their discovery?

It all started in 2000, when Professor Daniel Louvard, the former director of the Institut Curie Research Center, launched the PIC incentivizing programs, designed to stimulate collaboration between physicians and researchers on risky subjects. I got together with Professor Jean-Marc Cosset, then Director of the Department of Radiotherapy, to think about a project we might put forward for one of the programs. We were interested in resistance to radiotherapy, that is, the mechanisms that result in certain tumors remaining completely unaffected by radiotherapy. These resistance mechanisms primarily depend on the activation of DNA repair pathways. To counteract this resistance, we therefore imagined developing repair inhibitors.

It’s important to point out that we weren’t the only people focusing on repair inhibitors at that time. The big pharmaceutical labs were also starting to identify them. PARP inhibitors, which are now used in clinical practice, are from that generation. Since they only work for a small number of patients, we decided to develop a completely different technique, using another repair pathway. I had worked with small DNA molecules in the past, so I came up with the idea of using them as a repair inhibitor that would interfere with the recognition and location of damage.

What are your research activities at the moment?

I’m trying to understand the properties of these molecules and their mechanisms of action. But my team and I are also looking into whether there are any markers that would enable us to identify the patients who would benefit the most from Dbaits. Basically all the activities involved in the development of a therapeutic drug nowadays: finding the best protocols and identifying the sufferers who are most likely to benefit from the drugs. We need to be able to better diagnose patients in order to offer them the most suitable treatment.

 

What are the future challenges for radiotherapy?

I think there are two major challenges.

Firstly, it is still difficult to treat certain indications using radiotherapy: those close to at-risk organs (lungs, brain, liver etc.). To address this, we need to get better at controlling the beams and preventing side effects on the surrounding healthy tissue. We therefore need a form of radiotherapy that is less aggressive towards the neighboring tissue and organs. That’s what we’re working on with FLASH, and it can certainly be developed much further.

Secondly, we need to be able to identify the patients who are more sensitive to radiation than the general population and for whom treatments could be better adapted. We could then offer them alternative protocols.

Radiobiology research deserves our full attention. Following Marie Curie’s discoveries, physicists focused their efforts on the physics of radiation. But there is still much to do at the biological level, where research has focused primarily on pollution, accidents: low-dose but continuous exposure. Our efforts now need to be focused on using radiation for therapeutic purposes.

 

Marie Dutreix is CNRS Research Director and Head of the Recombination, Repair, and Cancer: From Molecule to Patient team (Inserm/CNRS/Institut Curie)

Improving radiotherapy

 

copyright: Uriel Chantraine / Institut Curie