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Targeting cardiomyopathies associated with RASopathies: the role of mitogen-activated protein kinase inhibitors and
Valentina Botia-Arciniegas1, Natalia Jimenez-Cardozo1,2, Juliana Lores1,2,3
1Department of Basic Sciences, Faculty of Health Sciences.
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.
Insights
RASopathies, genetic disorders affecting the RAS-mitogen-activated protein kinase (MAPK) pathway, can cause severe cardiomyopathies. Trametinib, a MEK inhibitor, shows promise as an effective treatment, offering new hope for patients with limited options.
Area of Science:
- Genetics
- Molecular Biology
- Cardiology
Background:
- RASopathies are rare genetic disorders stemming from mutations in the RAS-MAPK pathway.
- These mutations disrupt cellular processes, leading to multisystemic issues, notably cardiomyopathies, which significantly increase mortality.
- Current treatment options for RASopathy-associated cardiomyopathies are limited.
Purpose of the Study:
- To review the existing evidence on using MAPK inhibitors for treating cardiomyopathies in RASopathies.
- To assess the efficacy of trametinib, a MEK inhibitor, in managing these cardiac complications.
Main Methods:
- A systematic literature search was performed across PubMed, Scopus, and Embase.
- Studies reporting the use of MAPK inhibitors in RASopathy patients with cardiomyopathies were identified and analyzed.
Main Results:
- Nine studies encompassing 14 cases (9 Noonan syndrome, 5 Costello syndrome) were included.
- Successful treatment outcomes were reported with trametinib, a MEK inhibitor.
- This indicates a potential new therapeutic avenue for these complex conditions.
Conclusions:
- Trametinib, a MEK inhibitor, demonstrates therapeutic potential for cardiomyopathies in RASopathies.
- Further research into trametinib and other MAPK pathway inhibitors is crucial for improving patient survival and quality of life.
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