Revolutionary research in radiotherapy

02/06/2023
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Institut Curie's research teams are pioneers in the development of revolutionary radiotherapy modalities.

reportage radiothérapie JMC 2023

Although much progress has been made in terms of imaging precision, ballistics and dosimetry, new dose delivery methods, with new biological effects on tissues, are paving the way for promising therapeutic solutions to target tumors that until now have been radio-resistant, and to considerably reduce long-term after-effects. Institut Curie’s teams are pioneers in the emergence of revolutionary radiotherapy solutions.

Institut Curie’s DNA is that of an osmosis between interdisciplinary research and clinical practice. Original and promising therapies are emerging from this rivalry. Recent research breakthroughs at Institut Curie in physics and radiobiology, but also in terms of image analysis combined with artificial intelligence, pose new challenges which are creating a buzz in the international community

Prof. Alain Puisieux, Director of the Institut Curie Research Center.

Mini-beams: a true paradigm shift

A new dose delivery system has been discovered by the “New Approaches in Radiotherapy” team headed by Yolanda Prezado, a physicist and CNRS research director. Indeed, her team - SIRIC accredited (Integrated cancer research site) - is a pioneer in research on proton mini-beam radiotherapy (pMBRT): a strategy that uses submillimetric proton beams and is proving very promising for treating radioresistant tumors with a poor prognosis, particularly in pediatrics.

Our goal is to exploit the fact that by changing the physical parameters of radiation, in other words the way in which we deliver the dose, we can change the biological effects and thus improve treatments

Explains Yolanda Prezado.

This new cancer therapy approach is based on strong spatial modulation of the dose with alternating high and low doses, contrary to the uniform dose distributions used in standard radiotherapy. Recent preclinical work by her team shows that this pMBRT technique activates separate radiobiological mechanisms and reduces side effects which limit the effectiveness of irradiation in treatment of brain tumors. This new technique provides hope for tumors with a poor prognosis, in particular gliomas and certain pediatric cancers. The results showed significant reduction of after-effects (in terms of cognitive ability, memory, anxiety), encouraging for the preparation of clinical trials. The research also revealed good activation of the immune system, which paves the way for effective combinations with immunotherapy, including cell therapy.

FLASH radiotherapy causes a furor

Discovered in 2014 in Institut Curie laboratories at Orsay by the team of Vincent Favaudon, a radiobiology researcher at Inserm, “FLASH” is a radiotherapy technique where ultra-high dose rate irradiation (10 Gray or more, equal to the dose received in one week of conventional radiotherapy) is delivered in a fraction of a second, i.e. 1,000 to 10,000 times more intense than conventional radiotherapy. This technique destroys the tumor cells while sparing the healthy tissue and if the next research steps lead to approval for future clinical application, FLASH radiotherapy will provide new opportunities for cancer treatment. Studies are conducted on FLASH radiotherapy at Institut Curie, on different types of electron and proton particle accelerators.

Recent preclinical research conducted by the team of Yolanda Prezado in proton FLASH have revealed reduced toxicity compared with conventional proton therapy, in tumors of the central nervous system in young patients. Furthermore, there is considerable hope in the field of FLASH radiotherapy using very high energy electrons (VHEE). In the coming years, combining the FLASH effect with a very high energy electron source could revolutionize radiotherapy, by targeting deep tumors and avoiding complex surgery.

“Bait” molecules which increase the effectiveness of radiotherapy

At Institut Curie, the “Repair, Radiation and Innovative Anti-cancer Therapies” team, thanks to the work of Dr. Marie Dutreix, emeritus research director at the CNRS, has developed a unique new class of drugs, namely Dbait molecules, which increase the effectiveness of radiotherapy. When seeking to understand the resistance to radiation observed in almost 20% of patients, along with her team she developed these small molecules which resemble damaged DNA, tricking the cells into thinking that the quantity of damage to repair after radiotherapy or chemotherapy treatment is much higher than is actually the case.

The tumor cell, “overwhelmed” by the quantity of damage to be repaired, self-destructs. A clinical trial is currently underway with the biotech Onxeo with this innovative therapy, which represents major hope for the fight against high-risk pediatric cancer in particular.

Other teams at Institut Curie are involved in research particularly in imaging, IT, and mathematics. Since the future of anti-cancer therapies lies in combining treatments, a number of projects are underway at Institut Curie that combine radiotherapy-immunotherapy, radiotherapy and nanoparticles, FLASH and Dbaits, in order to build a battery of tools against cancer.