A latest research perspective was published in Oncotarget’s Volume 14 on May 4, 2023, entitled, “Targeting cellular respiration as a therapeutic strategy in glioblastoma.”

While glycolysis is abundant in malignancies, mitochondrial metabolism is important as well. Mitochondria harbor the enzymes relevant for cellular respiration, which is a critical pathway for each regeneration of reduction equivalents and energy production in the shape of ATP.

On this research perspective, researchers Enyuan Shang, Trang Thi Thu Nguyen, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus D. Siegelin from Columbia University Medical Center, City University of Recent York and Ulm University Medical Center discuss their recent finding that FDA-approved HDAC-inhibitors can have a profound impact on energy metabolism in solid tumor cells, including glioblastoma (GBM).

“Due to impact of HDAC-inhibitors on metabolism we hypothesized that imipridones, which suppress cellular respiration, might synergize with these compounds to significantly enhance killing of GBM cells. Indeed, we found that imipridones reversed HDAC-inhibitor induced activation of cellular respiration and in turn the mix treatment facilitated induction of intrinsic apoptosis in a way that was partially reliant on the anti-apoptotic Bcl-2 relations.”

The oxidation of NADH2 and FADH2 are fundamental since NAD and FAD are the important thing components of the TCA-cycle that’s critical to entertain biosynthesis in cancer cells. The TCA-cycle itself is predominantly fueled through carbons from glucose, glutamine, fatty acids and lactate.

Targeting mitochondrial energy metabolism appears feasible through several drug compounds that activate the CLPP protein or interfere with NADH-dehydrogenase, pyruvate-dehydrogenase, enzymes of the TCA-cycle and mitochondrial matrix chaperones. While these compounds have demonstrated anti-cancer effects in vivo, recent research suggests which patients almost definitely profit from such treatments.

“In summary, targeting tumor cell metabolism is relevant and future research must discover patient populations that particularly profit from such treatments. Furthermore, while most studies related to metabolism still rest predominantly on the tumor cells it’s critical to increase such observations to the microenvironment of the tumors, especially on the subject of the immune system.”

Source:

Journal reference:

Shang, E., et al. (2023) Targeting cellular respiration as a therapeutic strategy in glioblastoma. Oncotarget. doi.org/10.18632/oncotarget.28424.