4.4 Review

Metabolomics in paraganglioma: applications and perspectives from genetics to therapy

期刊

ENDOCRINE-RELATED CANCER
卷 30, 期 6, 页码 -

出版社

BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-22-0376

关键词

mass spectrometry; nuclear magnetic resonance spectroscopy; succinate dehydrogenase; fumarate hydratase; oncometabolites

向作者/读者索取更多资源

Metabolites play a crucial role in maintaining life and can be quantified to improve the diagnosis and treatment of pheochromocytoma/paraganglioma (PPGL). PPGLs have unique features that provide biomarkers and clues for targeted treatments. Genetic aberrations in PPGL alter cellular pathways and can be exploited diagnostically. Personalized diagnostics and treatment are within reach with the availability of omics technologies.
Metabolites represent the highest layer of biological information. Their diverse chemical nature enables networks of chemical reactions that are critical for maintaining life by providing energy and building blocks. Quantification by targeted and untargeted analytical methods using either mass spectrometry or nuclear magnetic resonance spectroscopy has been applied to pheochromocytoma/paraganglioma (PPGL) with the long-term goal to improve diagnosis and therapy. PPGLs have unique features that provide useful biomarkers and clues for targeted treatments. First, high production rates of catecholamines and metanephrines allow for specific and sensitive detection of the disease in plasma or urine. Secondly, PPGLs are associated with heritable pathogenic variants (PVs) in around 40% of cases, many of which occur in genes encoding enzymes, such as succinate dehydrogenase (SDH) and fumarate hydratase (FH). These genetic aberrations lead to the overproduction of oncometabolites succinate or fumarate, respectively, and are detectable in tumors and blood. Such metabolic dysregulation can be exploited diagnostically, with the aim to ensure appropriate interpretation of gene variants, especially those with unknown significance, and facilitate early tumor detection through regular patient follow-up. Furthermore, SDHx and FH PV alter cellular pathways, including DNA hypermethylation, hypoxia signaling, redox homeostasis, DNA repair, calcium signaling, kinase cascades, and central carbon metabolism. Pharmacological interventions targeted toward such features have the potential to uncover treatments against metastatic PPGL, around 50% of which are associated with germline PV in SDHx. With the availability of omics technologies for all layers of biological information, personalized diagnostics and treatment is in close reach.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据