Dr Max PIFFOUX (Center Léon Bérard, Lyon)

Doctor Max PIFFOUX - under the responsibility of the "Apoptosis and cancer" team coordinated by Aurélie DUTOUR at the CLB - is the scientific manager of the following research project: "Autophagic induction as a booster of response to immunotherapies: trial of a new therapeutic class, calorie restriction mimetics, in the pediatric osteosarcoma model ". Eva pour la vie & Aidons Marina have decided to co-finance the launch of this project, by providing a grant of 40,000 euros.
Dr Max Piffoux, you are both a medical student and a post-doctoral researcher at INSERM at INSERM in Lyon. You have decided to focus your research on osteosarcomas in children. Can you tell us more about this project, and your motivations for working on childhood cancer? Was it difficult to convince your team?
First of all, I want to clarify that I am not alone in leading this project, it is a team story! The origin of the project is above all a story of meetings, of shared enthusiasm, like many research stories. We have developed this project to confirm the interest of a new type of molecules to potentiate the effect of immunotherapies. They have the advantage of not having any side effects a priori, of being easy to administer by mouth. They have not yet been developed by drug manufacturers, but if this were the case they could quickly end up in clinical trials. At the start of this project, we were looking for a cancer model resistant to immunotherapy to confirm results obtained in other sarcomas. Among the cancers resistant to immunotherapy, osteosarcomas are particularly resistant, and affect a predominantly pediatric population. I was also made aware of the subject by my partner, a resident in pediatric orthopedic surgery and co-sponsor of the project. We are also working with a Parisian team specializing in this type of molecules. This made me understand that this pathology was particularly relevant from a scientific but also a medical point of view: resistance to immunotherapies, few therapeutic avenues, no change in care for 30 years ... unfortunately it is an area where there is still work to be done, a real challenge. I hope we can add a stone to the edifice.


What is the current therapeutic situation, and what are your hopes?

In osteosarcoma, treatment is currently based on surgery and chemotherapy. It is a very cumbersome protocol, but it works relatively well for some patients. If unfortunately patients do not respond or relapse, treatment options are very limited. I think that therapeutic innovation in the field will come either from the addition of molecules without side effects to the current treatment, or from new second-line approaches which, if they prove to be effective, could perhaps replace the first line. We see that in the second case the road is long. Instead, we chose to focus on the first option: developing non-toxic treatments in combination with the current treatment. We know that our "drug candidates" have shown their efficacy in another type of sarcoma resistant to immunotherapies, making it sensitive to immunotherapies when combined with chemotherapies, in particular those used for osteosarcomas. Our goal, if the results are promising in animals, is to set up a trial to test these molecules directly on the front line. However, we know that it takes a long time for a new treatment to arrive in a clinical trial, especially for these pathologies with few patients.


Do you plan to develop this project with other researchers and extend it to other types of pediatric cancers?
Of course ! More generally, we target cancers resistant to immunotherapy, including certain pediatric ones such as Ewing's sarcoma or neuroblastoma. The project is already made up of a team of researchers, but the door is intended to remain open.


Did you encounter any financial or administrative difficulties in launching this project? What does the financial support of Eva for Life and Aidons Marina allow you to do?
I must admit that since I arrived in Lyon a year and a half ago, I have been welcomed with open arms by the teams of the Center Léon Bérard. From a financial point of view, everything went well because the support of Eva for life and Aidons Marina was very quick to obtain! I think we underestimate the role of this kind of preliminary funding for young researchers, who spend their time looking for money at the expense of time spent doing research ... This will allow us, if the results are conclusive, to find funding to take this project further.


In addition to collecting donations, Eva pour la vie has launched a fundamental initiative aimed at encouraging the State to create a fund dedicated to research on childhood cancer, as well as to improve aid to families of children. sick children. A first victory, undoubtedly insufficient but unprecedented, was obtained at the end of 2018: the vote of a fund of 5 million euros / year for this research. What do you think ?
I think research in general needs support. The share of French GDP devoted to research, both public and private, is low compared to other comparable countries. Seen from inside the public system, researchers are paid to spend about 25 to 50% of their time looking for money to work. The creation of this fund is a great step forward!


What would you like to say to families whose children are battling cancer?
This is a more than difficult question! Wish them courage of course, but also thank them for their help. The research is unfortunately relatively slow, we put all our heart into it. Quick financial support like the one you give allows new avenues of research to emerge quickly.

WE ALSO SUPPORT ..

Dr Christophe GROSSET (INSERM Bordeaux)

Since 2012, Dr Christophe Grosset has been studying hepatoblastoma, a liver tumor that affects very young children. Today, the main difficulty is to treat patients suffering from metastases or from an inoperable tumor resistant to treatment. With the support of the Eva pour la vie association, the team has set up a new model of hepatoblastoma in the chick embryo which makes it possible to test the effectiveness of new therapeutic molecules (such as microRNAs) and of facilitate the study of these tumors in the laboratory. It has also shown the value of a drug already used in the treatment of certain leukaemias, to treat children with very aggressive liver cancer.

Dr Fabienne MEGGETTO (INSERM Toulouse)

Dr Fabienne Meggetto is research director at INSERM Toulouse, within a team of excellence whose research work focuses on lymphomas in children. The Eva pour la vie association has decided to provide aid of 50,000 euros for the start of an ambitious and transversal project, which could make it possible to find new therapeutic avenues for lymphomas with a poor prognosis, but also, others. solid tumors such as neuroblastoma. ...

Dr Annie SCHMIDT (INSERM Nice)

The preclinical research project of Dr Alliana Schmid's team focuses on the treatment of pulmonary metastases from osteosarcoma by combinations of immunotherapy.

The aim of this project, which is unique in France, is to evaluate, in a preclinical model of pulmonary metastases from osteosarcoma - a cancer with a poor prognosis which particularly affects adolescents - the effects of a treatment combining two complementary immunotherapy strategies. The Eva pour la vie association is providing funding of 50,000 euros over 3 years, representing the entire cost of this project.


Dr Eddy PASQUIER (CNRS Marseille)

Dr Pasquier's research work mainly focuses on the repositioning of drugs which consists of testing, in new therapeutic indications, drugs already approved by the health authorities. The aim of this work is to identify new therapeutic targets for the most difficult to treat cancers and thus improve the care of patients suffering from these aggressive forms and refractory to treatment . In particular, pediatric cancers (neuroblastoma), brain tumors affecting children as well as adults (glioblastoma, medulloblastoma) as well as certain rare forms of cancer (angiosarcoma).



Dr Marie CASTETS (INSERM Lyon)

The work of the INSERM team co-directed by Dr Marie Castets (CR1 Inserm, HDR) and Dr Jean-Yves Blay (PUPH, HDR) focuses on cell death and cancers. Thanks to the support of Eva pour la Vie (55,000 euros) and other associations, this team is currently developing these lines of research on rhabdomyosarcomas, osteosarcomas and neuroblastomas ...



Dr Martin HAGEDORN (INSERM Bordeaux)

Since September 2014, Dr Martin Hagedorn has been leading a team of researchers (Caroline CAPDEVIELLE , Farah RAHAL, Justine CHARPENTIER and Mélissa MENARD) which devotes its research work to the identification of new therapeutic targets in brainstem tumors and to the improvement of its treatment methods. Work recognized by several European scientific teams & experts.



Dr Patrick AUGUSTE (INSERM Bordeaux)

For more than 20 years, this teacher-researcher has been working on cancer. And it's been almost 10 years since he went to kidney cancer or renal cell carcinoma. By joining the team of Dr Christophe Grosset (Inserm, MiRCaDe team), he wanted to use his experience and take a new step forward by working on childhood cancer. He is the initiator of an ambitious project, which involves several surgeons, doctors and international researchers, on the study of nephroblastoma (or Wilms tumor) in children, co-funded by the association Eva pour la vie and Aidons Marina ...



Prof. Sébastien PAPOT (University of Poitiers)

At the end of 2018, the Nouvelle Aquitaine region agreed to co-finance with Eva for life the research project "Biological and preclinical studies of new anticancer agents, including some targeting EZH2 / PRC2, in the treatment of highly proliferating hepatoblastoma", led by Prof. Papot and Dr Grosset. The Eva pour la Vie association covered up to 50% of the cost of the purchase of laboratory equipment (in the amount of € 9,000) necessary for the smooth running of this work.

Dr Olivia FROMIGUE (Institut Gustave Roussy)

Resistance to treatment is a major clinical problem, in particular in the case of osteosarcomas, bone tumors affecting children or adolescents. Indeed, chemotherapy, associated with surgery, is the central pillar of current treatment. However, many osteosarcomas are or become resistant to these antiproliferative drugs. Recurrences and / or the appearance of metastases are then frequent. 2 out of 5 patients cannot be cured! Osteosarcoma is therefore a pediatric cancer with a poor prognosis for which it is absolutely necessary to identify ways to counteract resistance to treatment in order to improve the chances of recovery for patients.



Epidemiological research

If the development of therapeutic routes adapted to the child is essential (to try to save the children who today, remain without a therapeutic solution and / or to reduce the side effects), we do not forget an equally strong reality: over the past 50 years, the number of children affected by cancer has never declined. Much remains to be done in terms of prevention, both in terms of research and regulation. Eva pour la vie is actively involved by co-financing environmental studies. The first of these, HAPPI, aimed to have the KUDZU SCIENCE laboratory analyze dust samples taken in homes bordering vines - welcoming children or pregnant women - as well as in a primary school classroom.