Molecular pathways and possible therapies for head and neck vascular anomalies

Abstract

Vascular anomalies are a heterogenous group of vascular lesions that can be divided, according to the International Society for the Study of Vascular Anomalies Classification, into two main groups: vascular tumors and vascular malformations. Vascular malformations can be further subdivided into slow-flow and fast-flow malformations. This clinical and radiological classification allows for a better understanding of vascular anomalies and aims to offer a more precise final diagnosis. Correct diagnosis is essential to propose the best treatment, which traditionally consists of surgery, embolization, or sclerotherapy. Since a few years, medical treatment has become an important part of multidisciplinary treatment. Genetic and molecular knowledge of vascular anomalies are increasing rapidly and opens the door for a molecular classification of vascular anomalies according to the underlying pathways involved. The main pathways seem to be PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Knowing the underlying molecular cascades allows us to use targeted medical therapies. The first part of this article aims to review the vascular anomalies seen in the head and neck region and their underlying molecular causes and involved pathways. The second part will propose an overview of the available targeted therapies based on the affected molecular cascade. This article summarizes theragnostic treatments available in vascular anomalies.

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“…The development of OSCC is often related to change in molecular level of the receptor tyrosine kinase (RTK), PI3K/AKT, and p53 pathway, and G1/S cell cycle transition [ 31 - 33 ]. The PI3K family kinases are lipid kinases comprising of the catalytic subunits (p110α, p110β, p110δ and regulatory subunits (p85α, p85β, p55γ, p55α, p50α) and are downstream of RTKs.…”

NRASQ61R mutation drives elevated angiopoietin‐2 expression in human endothelial cells and a genetic mouse model

“…The identification of somatic mutations in vascular anomalies offers an opportunity to uncover disease-causing pathways and develop new targeted therapies, which will require preclinical cell and animal models carrying these mutations. 25,26 KLA patients often have the NRAS Q61R mutation in lesion tissue 27 and elevated blood Ang-2 levels. 18,19 However, whether these are directly related was unclear, as these patients have a complex pathophysiology.…”

Overview of peripheral arteriovenous malformations: From diagnosis to treatment methods

“… 5 Additionally, partial somatic mutations and abnormal signaling pathways that can potentially induce endothelial cell dysfunction have been observed in sporadic AVMs. 6 Researchers have suggested that MAP2K1 gene mutations may be related to sporadic AVM onset, 1 along with the implication of RASA1 , EPHB4 , ENG , BMP9 , ACVRL1 , SMAD4 , and BMPR2 gene mutations in AVM-related disorders. 5 Moreover, researchers investigating the molecular mechanisms of AVMs have proposed rapamycin or trimetinib as potential target drugs to treat AVMs 7 , 8 ; however, more investigations are required to support this strategy.…”