PDF(Pubmed)
Abstract：
The RASopathies are a group of clinically defined developmental syndromes caused by germline variants of the RAS/mitogen-activated protein (MAPK) cascade. The prototypic RASopathy is Noonan syndrome, which has phenotypic overlap with related disorders such as cardiofaciocutaneous syndrome, Costello syndrome, Noonan syndrome with multiple lentigines, and others. In this state-of-the-art review, we summarize current knowledge on unmet therapeutic needs in these diseases and novel treatment approaches informed by insights from RAS/MAPK-associated cancer therapies, in particular through inhibition of MEK1/2 and mTOR in patients with severe disease manifestations. We explore the possibilities of integrating a larger arsenal of molecules currently under development into future care plans. Lastly, we describe both medical and ethical challenges and opportunities for future clinical trials in the field.
摘要：
放射病是一组临床定义的发育综合征，由RAS/丝裂原活化蛋白（MAPK）级联的种系变体引起。原型RASopathy是Noonan综合征,与心脏皮肤综合征等相关疾病有表型重叠，科斯特洛综合征,努南综合征伴多个腹水,和其他人。在这份最新的审查中，我们总结了有关这些疾病中未满足的治疗需求的最新知识，以及通过RAS/MAPK相关癌症疗法的见解获得的新治疗方法。特别是通过在有严重疾病表现的患者中抑制MEK1/2和mTOR。我们探索了将目前正在开发的更大分子库整合到未来护理计划中的可能性。最后,我们描述了医学和伦理方面的挑战以及该领域未来临床试验的机遇.
