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A new study reveals an increased function for metabolic enzymes in kidney cancer

Nov, 2021

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A group of researchers identified that the under-expression of a certain metabolic enzyme is a prevalent and detrimental epigenetic modifying characteristic in clear cell renal cell carcinoma.

The results indicate that efficient deficiency of the enzyme succinate dehydrogenase is a common characteristic of ccRCC, which reports for 80% of kidney cancers and is just not restricted to 0.05 to 0.5% of kidney cancers with SDH germline mutations, as the WHO currently classifies them. SDH is the first identified metabolic enzyme that participates in both the electron transport chain and the TCA cycle, both of which are required for cells in creating and releasing energy.

The reduced SDH activity limits the metabolic conversion of succinate to fumarate in the TCA cycle, resulting in succinate buildup, which has oncogenic implications via epigenetic regulation, as underlined more in the present research. WHO classification of kidney malignancies in 2016 distinguishes SDH-deficient renal carcinoma as a distinct entity, relating primarily to kidney cancers linked with germline mutations in any of SDH subunits, which account for 0.05 to 0.5 % of all kidney cancers.

Researchers used numerous molecular biology tools to analyze ccRCC tumor cell lines, primary tumor tissues, and data from The Cancer Genome Atlas program to further assess the overall function of SDH depletion in kidney cancer development and progression. The researchers discovered that SDH deficiency was present in the majority of cases with ccRCC, which caused around 80% of kidney cancers and is related to negative epigenetic effects. Moreover, SDH deficiency was linked to decreased total and disease-free lifespan in such patients.

The researchers then began discussing the molecular pathways that contribute to SDH downregulation in ccRCC, as well as the negative biological effects of the downregulation. The studies prompted the researchers to request that the WHO rename the entity SDH-deficient renal carcinoma as SDH germline mutation-associated renal carcinoma, for both nomenclature correctness and to simplify things in identifying a group of patients with kidney cancer with different pathologic and clinical appearances.

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