| Literature DB >> 29899452 |
Quitterie Venot1, Thomas Blanc1,2,3, Smail Hadj Rabia2,4,5, Laureline Berteloot5,6, Sophia Ladraa1, Jean-Paul Duong2,7, Estelle Blanc8, Simon C Johnson9, Clément Hoguin1, Olivia Boccara4, Sabine Sarnacki2,3, Nathalie Boddaert2,5,6, Stephanie Pannier2,10, Frank Martinez11, Sato Magassa1, Junna Yamaguchi1, Bertrand Knebelmann1,2,11, Pierre Merville12,13, Nicolas Grenier14, Dominique Joly1,2,11, Valérie Cormier-Daire2,5,15, Caroline Michot2,5,15, Christine Bole-Feysot5, Arnaud Picard2,16, Véronique Soupre16, Stanislas Lyonnet2,5,15, Jeremy Sadoine17, Lotfi Slimani17, Catherine Chaussain2,17, Cécile Laroche-Raynaud18, Laurent Guibaud19, Christine Broissand20, Jeanne Amiel2,5,15, Christophe Legendre1,2,11, Fabiola Terzi1,2, Guillaume Canaud21,22,23.
Abstract
CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.Entities:
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Year: 2018 PMID： 29899452 PMCID： PMC7610773 DOI： 10.1038/s41586-018-0217-9
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962