Indirect inhibitor of cellular respiration for treatment of glioblastoma

A new research perspective Oncotarget’s Volume 14, published May 4, 2023, titled “Targeting Cellular Respiration as a Treatment Strategy for Glioblastoma”.

Although glycolysis is prevalent in malignant tumors, mitochondrial metabolism is equally important. Mitochondria harbor enzymes associated with cellular respiration and are important pathways for both regeneration of reducing equivalents and energy production in the form of ATP.

From the perspective of this study, researchers Enyuan Shang, Trang Thi Thu Nguyen, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus D. Siegelin Researchers from Columbia University Medical Center, City University of New York, and Ulm University Medical Center found that FDA-approved HDAC inhibitors could profoundly affect energy metabolism in solid tumor cells, including glioblastoma (GBM). Discuss the recent discovery that there is

“Because of the effects of HDAC inhibitors on metabolism, we hypothesized that imipridone, which suppresses cellular respiration, might synergize with these compounds to significantly enhance GBM cell death. We reversed the activation of cellular respiration caused by HDAC inhibitors, and then the combination treatment enhanced the induction of endogenous apoptosis in a manner that was partially dependent on the anti-apoptotic Bcl-2 family members.”

Oxidation of NADH2 and FADH2 is fundamental, as NAD and FAD are key components of the TCA cycle that are essential for cancer cell biogenesis. The TCA cycle itself is primarily fueled by carbon from glucose, glutamine, fatty acids and lactate.

We believe that targeting mitochondrial energy metabolism is feasible through several drug compounds that either activate CLPP proteins or interfere with NADH dehydrogenase, pyruvate dehydrogenase, enzymes of the TCA cycle, and mitochondrial matrix chaperones. can be Although these compounds have demonstrated anti-cancer effects, in vivorecent research suggests which patients are most likely to benefit from such treatment.

“In summary, targeting tumor cell metabolism is important and future studies should identify patient populations that would particularly benefit from such treatment. Furthermore, most studies related to metabolism are Although still primarily based on tumor cells, it is important to extend such observations to the microenvironment” with respect to tumors, particularly the immune system. ”


Reference magazine:

Shan, E., other. (2023) Targeting cellular respiration as a therapeutic strategy for glioblastoma. Oncotarget.

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