Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum
| Affiliation auteurs | !!!! Error affiliation !!!! |
| Titre | Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum |
| Type de publication | Journal Article |
| Year of Publication | 2019 |
| Auteurs | Parker VER, Keppler-Noreuil KM, Faivre L, Luu M, Oden NL, De Silva L, Sapp JC, Andrews K, Bardou M, Chen KY, Darling TN, Gautier E, Goldspiel BR, Hadj-Rabia S, Harris J, Kounidas G, Kumar P, Lindhurst MJ, Loffroy R, Martin L, Phan A, Rother KI, Widemann BC, Wolters PL, Coubes C, Pinson L, Willems M, Vincent-Delorme C, Vabres P, Semple RK, Biesecker LG, Grp PROMISEWorking |
| Journal | GENETICS IN MEDICINE |
| Volume | 21 |
| Pagination | 1189-1198 |
| Date Published | MAY |
| Type of Article | Article |
| ISSN | 1098-3600 |
| Mots-clés | mosaicism, overgrowth, PIK3CA, sirolimus |
| Résumé | {Purpose: PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110 alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth. Methods: Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Results: Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (SD 16.0 |
| DOI | 10.1038/s41436-018-0297-9 |