Project description
Novel treatments for overgrowth syndromes
Overgrowth syndromes (OS) are rare genetic disorders usually characterised by mutations in the PIK3CA/AKT/mTOR pathway, which plays a key role in cell proliferation. OS patients with PIK3CA gain-of-function mutation (PROS) exhibit severe disabilities which may lead to premature death. PROSPECTS is an EU-funded initiative that aims to address the lack of treatments for PROS patients. Previous work had shown very promising clinical results for BYL719, a novel PIK3CA inhibitor. The project aims to extend these findings to the discovery of other treatments by investigating the pathophysiology of PROS and identifying disease-specific biomarkers. Candidate treatments may slow down the progression of PROS and also find application in oncology.
Objective
Overgrowth syndromes (OS) are rare genetic disorders that can be either localized or generalized. In most cases, the mutations are not inherited but occur during embryogenesis leading to somatic mosaicism. The genes involved in OS are not well characterized but most appear to be part of the PIK3CA/AKT/mTOR pathway, a major actor in cell growth and proliferation. Among the different genes, gain-of-function mutations of PIK3CA have a prominent role. Patients with PIK3CA gain of function mutation (PROS) usually have complex tissue malformations, including abnormal vessels, anarchic adipose tissue, muscle hypertrophy and/or bone deformation. Currently, there are no specific treatments for PROS patients. Patients mainly receive supportive care including debulking surgery, sclerotherapy and nutritional support. PROS often result in severe disabilities with deleterious social consequences and premature death. We recently generated a mouse model of PROS that, for the 1st time, recapitulates the patient phenotype, identified BYL719, a PIK3CA inhibitor undergoing development in oncology, as a potential therapeutic for PROS and demonstrated the efficacy of this drug in our mouse model (Venot et al, Nature 2018). Based on these very promising results, we were authorized to treat adults and children suffering from very severe forms of PROS. The clinical outcome is very promising. Now, in this project, we will decipher the physiopathology of PROS, identify biomarkers and new treatments. To this aim, we will combine in vitro and in vivo approaches using very innovative technologies and new mouse models of OS. Consistently with my previous works, we will extend our findings to Human through our unique PROS Biobank. The accomplishment of this project may lead to the discovery of novel therapeutic targets and strategies to slow down the progression of PROS. But, more importantly, based on the pleiotropic role by PI3KCA in cancer, our findings will open new perspectives in oncology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine surgery
- natural sciences biological sciences developmental biology
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-COG
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75006 PARIS
France
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