Targeting cardiomyopathies associated with RASopathies: the role of mitogen-activated protein kinase inhibitors and therapeutic challenges.

Abstract

RASopathies are rare genetic disorders caused by germline mutations in genes that regulate the RAS-mitogen-activated protein kinase (MAPK) pathway, a critical pathway involved in various cellular processes. Disruption of this pathway leads to multisystemic manifestations, including cardiomyopathies, a cause of high morbi-mortality. In response to the urgent need to improve survival in patients with RASopathies, alternative therapies, such as MAPK inhibitors traditionally used in cancer treatment, have been explored. This article reviews the current evidence on the use of these medications in treating cardiomyopathies associated with RASopathies. The search was conducted in the PubMed, Scopus, and Embase databases identifying nine studies reporting a total of 14 cases (nine with Noonan syndrome and five with Costello syndrome) where patients were successfully treated with trametinib, a MEK inhibitor. This therapeutic alternative broadens the horizons of opportunity for patients who often face limited options for enhancing their quality of life. Therefore, it is important to prioritize ongoing research in this field, focusing not only on further investigation on trametinib, but also exploring other potential therapeutic approaches.