image: KRAS mutated endothelium promotes the occurrence and development of AVMs through a variety of ways, including promoting EndMT, angiogenesis, VEGF signaling pathway and pericyte loss. KRAS mutation in endothelial cells activates the MEK/ERK pathway, but has no direct effect on PI3k. Subsequently, KRAS/BRAF activates the Notch pathway or TGFb/BMP pathway through the MEK/ERK pathway, thereby affecting endothelial cell function. It is worth noting that these mutated endothelial cells also release vesicles that affect normal endothelial cells.
Credit: Dr. Yong Cao and Dr. Jizong Zhao
Cerebral vascular malformations (CVMs), including cerebral arteriovenous malformations (AVMs) and cavernous malformations (CCMs), have long posed challenges due to their complex origins and severe clinical implications. This comprehensive review, authored by an expert team at Beijing Tiantan Hospital, redefines CVMs as genetic and molecular-driven conditions, departing from the traditional view of congenital structural anomalies.
The authors discuss innovative diagnostic approaches such as next-generation sequencing and non-invasive imaging genomics, revealing key somatic mutations like KRAS, BRAF, and PIK3CA that drive CVM pathogenesis. These discoveries have opened avenues for targeted therapies, including MEK inhibitors and mTOR inhibitors, promising effective alternatives to traditional surgical methods.
The study also explores cutting-edge techniques, including liquid and endovascular biopsies, to facilitate dynamic monitoring and early detection of CVMs. These methods, combined with artificial intelligence-driven genomic imaging, are paving the way for personalized treatments.
"This paradigm shift in understanding and treating CVMs marks a new era of precision medicine, with the potential to transform patient outcomes," says Dr. Yong Cao, co-lead author of the review. The study underscores the critical role of integrating genetic, molecular, and imaging advances into clinical practice.
Published in MedComm, the review calls for continued research and collaboration to address the challenges of CVM management and to bring innovative therapies to clinical application.
See the article:
Cerebral Vascular Malformations: Pathogenesis and Therapy
http://dx.doi.org/10.1002/mco2.70027
Journal
MedComm
Article Title
Cerebral vascular malformations: pathogenesis and therapy
Article Publication Date
8-Dec-2024