The RASopathies: from pathogenetics to therapeutics
The RASopathies are a group of disorders caused by a germline mutation in one of the genes encoding a component of the RAS/MAPK pathway. These disorders, including neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome and Legius syndrome, among others, have over...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2022-02-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/15/2/dmm049107 |
| _version_ | 1811332504240521216 |
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| author | Katie E. Hebron Edjay Ralph Hernandez Marielle E. Yohe |
| author_facet | Katie E. Hebron Edjay Ralph Hernandez Marielle E. Yohe |
| author_sort | Katie E. Hebron |
| collection | DOAJ |
| description | The RASopathies are a group of disorders caused by a germline mutation in one of the genes encoding a component of the RAS/MAPK pathway. These disorders, including neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome and Legius syndrome, among others, have overlapping clinical features due to RAS/MAPK dysfunction. Although several of the RASopathies are very rare, collectively, these disorders are relatively common. In this Review, we discuss the pathogenesis of the RASopathy-associated genetic variants and the knowledge gained about RAS/MAPK signaling that resulted from studying RASopathies. We also describe the cell and animal models of the RASopathies and explore emerging RASopathy genes. Preclinical and clinical experiences with targeted agents as therapeutics for RASopathies are also discussed. Finally, we review how the recently developed drugs targeting RAS/MAPK-driven malignancies, such as inhibitors of RAS activation, direct RAS inhibitors and RAS/MAPK pathway inhibitors, might be leveraged for patients with RASopathies. |
| first_indexed | 2024-04-13T16:37:09Z |
| format | Article |
| id | doaj.art-499ee81276df40caa1190455b8675e76 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-13T16:37:09Z |
| publishDate | 2022-02-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-499ee81276df40caa1190455b8675e762022-12-22T02:39:23ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112022-02-0115210.1242/dmm.049107049107The RASopathies: from pathogenetics to therapeuticsKatie E. Hebron0Edjay Ralph Hernandez1Marielle E. Yohe2 Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA The RASopathies are a group of disorders caused by a germline mutation in one of the genes encoding a component of the RAS/MAPK pathway. These disorders, including neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome and Legius syndrome, among others, have overlapping clinical features due to RAS/MAPK dysfunction. Although several of the RASopathies are very rare, collectively, these disorders are relatively common. In this Review, we discuss the pathogenesis of the RASopathy-associated genetic variants and the knowledge gained about RAS/MAPK signaling that resulted from studying RASopathies. We also describe the cell and animal models of the RASopathies and explore emerging RASopathy genes. Preclinical and clinical experiences with targeted agents as therapeutics for RASopathies are also discussed. Finally, we review how the recently developed drugs targeting RAS/MAPK-driven malignancies, such as inhibitors of RAS activation, direct RAS inhibitors and RAS/MAPK pathway inhibitors, might be leveraged for patients with RASopathies.http://dmm.biologists.org/content/15/2/dmm049107cardiofaciocutaneous syndromecostello syndromelegius syndromenoonan syndromerasrasopathies |
| spellingShingle | Katie E. Hebron Edjay Ralph Hernandez Marielle E. Yohe The RASopathies: from pathogenetics to therapeutics Disease Models & Mechanisms cardiofaciocutaneous syndrome costello syndrome legius syndrome noonan syndrome ras rasopathies |
| title | The RASopathies: from pathogenetics to therapeutics |
| title_full | The RASopathies: from pathogenetics to therapeutics |
| title_fullStr | The RASopathies: from pathogenetics to therapeutics |
| title_full_unstemmed | The RASopathies: from pathogenetics to therapeutics |
| title_short | The RASopathies: from pathogenetics to therapeutics |
| title_sort | rasopathies from pathogenetics to therapeutics |
| topic | cardiofaciocutaneous syndrome costello syndrome legius syndrome noonan syndrome ras rasopathies |
| url | http://dmm.biologists.org/content/15/2/dmm049107 |
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