{"id":42,"date":"2022-08-04T04:22:10","date_gmt":"2022-08-04T04:22:10","guid":{"rendered":"https:\/\/leapfrogbio.wpengine.com\/?page_id=42"},"modified":"2025-12-01T13:25:50","modified_gmt":"2025-12-01T21:25:50","slug":"science","status":"publish","type":"page","link":"https:\/\/www.leapfrog.bio\/fr\/science\/","title":{"rendered":"Recherche"},"content":{"rendered":"

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Recherche<\/h1>\n<\/div><\/div><\/div><\/div><\/div>

S\u2019attaquer aux mutations avec perte de fonction dans le cancer<\/h2>\n<\/div>

Des progr\u00e8s consid\u00e9rables ont \u00e9t\u00e9 r\u00e9alis\u00e9s dans notre compr\u00e9hension et le traitement du cancer. Diff\u00e9rentes approches biologiques et th\u00e9rapeutiques ont permis d\u2019am\u00e9liorer de fa\u00e7on significative les r\u00e9sultats cliniques. Certaines des avanc\u00e9es les plus marquantes reposent sur des th\u00e9rapies cibl\u00e9es con\u00e7ues pour traiter des cancers associ\u00e9s \u00e0 des mutations causales sp\u00e9cifiques dans des g\u00e8nes cl\u00e9s, appel\u00e9s g\u00e8nes conducteurs.<\/p>\n<\/div>

Ces th\u00e9rapies ont g\u00e9n\u00e9ralement \u00e9t\u00e9 d\u00e9velopp\u00e9es pour traiter des cancers associ\u00e9s \u00e0 des mutations avec gain de fonction dans des g\u00e8nes conducteurs, qui favorisent l\u2019apparition et la progression de la maladie. Leur objectif est d\u2019inhiber la fonction nouvellement acquise du g\u00e8ne ou les voies de signalisation qu\u2019il active. Les g\u00e8nes conducteurs pr\u00e9sentant des mutations avec gain de fonction, aussi appel\u00e9s oncog\u00e8nes, sont responsables d\u2019environ 30 % des cancers.\n\nLa majorit\u00e9 des autres cancers sont plut\u00f4t li\u00e9s \u00e0 des mutations avec perte de fonction dans des g\u00e8nes conducteurs qui, en temps normal, jouent un r\u00f4le de suppression tumorale. Ces g\u00e8nes, appel\u00e9s g\u00e8nes suppresseurs de tumeurs, ne peuvent pas \u00eatre cibl\u00e9s directement lorsqu\u2019ils sont mut\u00e9s, puisque leur fonction est d\u00e9j\u00e0 inactive.<\/p>\n<\/div><\/div><\/div>

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Acc\u00e9l\u00e9rer les avanc\u00e9es en l\u00e9talit\u00e9 synth\u00e9tique<\/h2>\n<\/div>

La l\u00e9talit\u00e9 synth\u00e9tique offre une voie prometteuse pour traiter les cancers associ\u00e9s \u00e0 des mutations avec perte de fonction. Une relation de l\u00e9talit\u00e9 synth\u00e9tique se produit lorsque la perte de fonction simultan\u00e9e de deux g\u00e8nes entra\u00eene la mort cellulaire, alors que la perte de fonction d\u2019un seul de ces g\u00e8nes n\u2019a pas cet effet.\n\nComme les cellules canc\u00e9reuses pr\u00e9sentent d\u00e9j\u00e0 des alt\u00e9rations g\u00e9n\u00e9tiques, une strat\u00e9gie consiste \u00e0 identifier puis \u00e0 cibler pharmacologiquement un partenaire synth\u00e9tiquement l\u00e9tal d\u2019un de ces g\u00e8nes. Les th\u00e9rapies reposant sur cette approche, comme les inhibiteurs de PARP, permettent de traiter efficacement certains cancers tout en limitant les effets toxiques sur les cellules normales.<\/p>\n<\/div><\/div><\/div><\/div><\/div>

R\u00e9inventer les approches traditionnelles de l\u00e9talit\u00e9 synth\u00e9tique<\/h2>\n<\/div>
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Leapfrog red\u00e9finit la fa\u00e7on dont les th\u00e9rapies cibl\u00e9es sur le plan g\u00e9n\u00e9tique sont d\u00e9couvertes pour les cancers associ\u00e9s \u00e0 des mutations avec perte de fonction. Les approches conventionnelles de l\u00e9talit\u00e9 synth\u00e9tique reposent sur des invalidations g\u00e9n\u00e9tiques, \u00e0 la fois pour reproduire la mutation causale et pour \u00e9valuer des cibles th\u00e9rapeutiques potentielles.\n\nOr, les m\u00e9dicaments reproduisent rarement les effets d\u2019une invalidation g\u00e9n\u00e9tique et peuvent avoir des impacts cliniquement significatifs qui ne sont pas observ\u00e9s avec ce type d\u2019approche. Notre plateforme OncoSLX surmonte ces limites gr\u00e2ce \u00e0 une strat\u00e9gie pharmacog\u00e9n\u00e9tique avanc\u00e9e et hautement optimis\u00e9e, qui permet d\u2019\u00e9valuer l\u2019ensemble des effets biologiques des m\u00e9dicaments en synergie avec les m\u00eames perturbations causales qui sont \u00e0 l\u2019origine des tumeurs humaines.<\/p>\n<\/div>

Les m\u00e9dicaments font bien plus que simplement \u00e9liminer une prot\u00e9ine : ils peuvent bloquer des activit\u00e9s enzymatiques sp\u00e9cifiques, moduler des domaines fonctionnels distincts, modifier des \u00e9tats de modification post-traductionnelle propres \u00e0 certains contextes cellulaires ou encore inhiber simultan\u00e9ment plusieurs prot\u00e9ines.\n\nLes inhibiteurs de PARP illustrent bien ce principe : leur forte synergie avec la perte de fonction de BRCA1 ne repose pas sur une simple reproduction d\u2019une invalidation de PARP1, mais sur leur capacit\u00e9 \u00e0 pi\u00e9ger PARP sur l\u2019ADN \u2014 un m\u00e9canisme qui \u00e9chappe aux approches classiques de l\u00e9talit\u00e9 synth\u00e9tique.\n\nEn testant directement la biologie des m\u00e9dicaments en fonction des v\u00e9ritables mutations conductrices, OncoSLX permet de capter ces nuances pharmacologiques et de g\u00e9n\u00e9rer des r\u00e9sultats qui se traduisent en b\u00e9n\u00e9fices pour les patients.<\/p>\n<\/div><\/div><\/div>

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