The RASopathies: from pathogenetics to therapeutics.
The RASopathies: from pathogenetics to therapeutics.
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DOI：
10.1242/dmm.049107
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发表时间：
2022-02-01
影响因子：
4.3
通讯作者：
Yohe ME
中科院分区：
文献类型：
--
作者：
Hebron KE;Hernandez ER;Yohe ME
RAS病是由编码RAS/MAPK通路组分的基因之一的种系突变引起的一组疾病。这些疾病，包括1型神经纤维瘤病、努南综合征、心面皮肤综合征、科斯特洛综合征和Legius综合征等，由于RAS/MAPK功能障碍而具有重叠的临床特征。虽然几种RASopathies非常罕见，但总体而言，这些疾病相对常见。在这篇综述中，我们讨论了RASopathy相关的遗传变异的发病机制，以及从研究RASopathies中获得的有关RAS/MAPK信号传导的知识。我们还描述了RASopathies的细胞和动物模型，并探讨新兴的RASopathy基因。还讨论了靶向药物作为RASopathies治疗的临床前和临床经验。最后，我们回顾了最近开发的靶向RAS/MAPK驱动的恶性肿瘤的药物，如RAS激活抑制剂，直接RAS抑制剂和RAS/MAPK通路抑制剂，可能是如何利用与RASopathies患者。概述：RAS病是由RAS/MAPK通路基因的生殖系致病性变异引起的发育障碍。在这里，我们回顾了临床前研究，这些研究为未来RASopathy患者的干预性临床试验提供了基础。
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. Summary: RASopathies are developmental disorders caused by germline pathogenic variants in RAS/MAPK pathway genes. Here, we review the preclinical studies that provide the basis for future interventional clinical trials for RASopathy patients.
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影响因子：
2
作者：
Bertola, Debora R.;Yamamoto, Guilherme L.;Pereira, Alexandre C.
通讯作者：
Pereira, Alexandre C.
影响因子：
15.9
作者：
Chen, Peng-Chieh;Wakimoto, Hiroko;Kucherlapati, Raju
通讯作者：
Kucherlapati, Raju
影响因子：
56.9
作者：
Castel, Pau;Cheng, Alice;McCormick, Frank
通讯作者：
McCormick, Frank
K-RAS前化作为潜在的抗癌靶标。
DOI：
10.1007/s10555-020-09902-w
发表时间：
2020-12
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
Baranyi M;Buday L;Hegedűs B
通讯作者：
Hegedűs B
影响因子：
11.2
作者：
Brady DC;Crowe MS;Greenberg DN;Counter CM
通讯作者：
Counter CM