Interview du Mois :

Dr Gilles PAGÈS,

Chef d'Equipe à l'IRCAN « Normal and pathological angiogenesis »

Angiogenesis is the physiological process through which new blood vessels form pre-existing vessels. There are many known factors that prompt angiogenesis in tumors. In the last 40 years researchers seriously considered blocking the process of angiogenesis as a medical treatment both for cancer and a subset of diseases caused by faulty angiogenesis. Using new medical treatments that either inhibit or stimulate angiogenesis, allows the prolongation of cancer patient’s lives, prevention of limb amputations, reversion of vision loss and improvement of general health. More than $4 billion has been invested in research and development angiogenesis-based medicines, making this area one of the most heavily of medical research in human history.

Gilles Pagès, team leader at IRCAN, is since January the President of the French Society of Angiogenesis. This is the perfect occasion for a quick interview with him, to talk about angiogenesis, major discoveries and future goals in this field.

Q: Your group “Normal and pathological angiogenesis”, created in 1999, has been focused on the understanding of the initiation and progression of abnormal angiogenesis. What is for you, your most important contribution in this field ?

Gilles Pagès (GP): One of the main contributions was the demonstration that the RAS/MAP Kinase pathway, which is constitutively active in more than 50% of tumors, stimulates VEGF expression. We deciphered the molecular mechanisms involved in this up-regulation (stimulation of the phosphorylation of Sp1/Sp3 transcription factors resulting in enhanced transcription of the vegf gene; increase of the mRNA half-life depending on the binding of specific proteins on AU rich sequences present in the 3’UTR of VEGF mRNA).

Q: Part of your team work is based on the development of new anti-angiogenic therapeutic strategies. Is your emplacement at an oncologic center an important factor for this particular line of work?

GP: Localization in the Cancer Centre of Nice (Centre Antoine Lacassagne, CAL) is really an added value. Intense discussions with physicians serve to focus on the pathology and the final goal which is to improve patients’ care.

Q: Translational research is on the hype, but concretely, what are the basis of your collaboration with clinicians?

GP: The basis of the collaboration is to have access to tumor samples collections from patients that are treated with new targeted therapies. These specific samples and the know-how of pathologists create, with the researchers of IRCAN, a real virtuous circle. CAL is also a reference centre for the use of proton therapy. This new protocol of radiotherapy is ongoing and we have access to the different machines for specific translational projects.

Q: Was your nomination for the presidency of the French Society of Angiogenesis something that you expected? Or was it something that surprised you?

GP: I was the delegate president for more than 4 years after the organization of the annual congress of the society in Monaco in 2012, which was a real success. The members of the administrative councils have unanimously voted for me in January. According to our status, I am elected for two years, with the possibility of a new term as president for two years.

Q: What are the main objectives of this society?

GP: The main objective is to promote all the disciplines of angiogenesis from physiological to pathological aspects. To do so, the congress of the society is organized every 18 months. My goal is also to extend the society to become the european or international society of angiogenesis from the core of the french society.

Q: What words of encouragement would you give to young scientists who might be envisioning a career in the field of angiogenesis? And what are the main obstacles that research in this field will face in the next 5–10 years?

GP: Making science is difficult in general and not only in the field of angiogenesis. Young scientists have to be enthusiastic, hard workers and have to develop many skills from molecular biology, to cell biology, biochemistry, informatics... The field of angiogenesis has been revolutionized by the discovery of VEGF and all the treatments dedicated to inhibit its pathological effects, especially in cancer and eye diseases. Developing new vessels is also a therapeutic goal for ischemic diseases. However, in both cases, the results were disappointing. I am still convinced that angiogenesis can be targeted for specific diseases. The main goal will be to adapt the treatments and to personalize them.

Thank you for your time!

Mai 2016