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Scientists use human iPSC-derived cells to model human disease in the lab without relying on hard to source patient-derived cells or inaccurate animal models. Watch this expert interview with Dr Will Bernard to get a primer on the latest innovations in in vitro human cell technology, and learn how scientists are adopting these new tools to simplify and standardize experiments in human disease research, and drug discovery.

Revolutionising in vitro Disease Models with iPSC Reprogramming Technology

Oncotarget

Oncotarget published this trending research perspective on May 4, 2023 in Volume 14, entitled, “Targeting cellular respiration as a therapeutic strategy in glioblastoma" by researchers from the Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY; Department of Biological Sciences, Bronx Community College, City University of New York, NY; Department of Neurosurgery, Ulm University Medical Center, Ulm 89081, Germany; Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm 89081, Germany.
 
DOI - https://doi.org/10.18632/oncotarget.28424

Correspondence to - Markus D. Siegelin -  ms4169@cumc.columbia.edu

Abstract

While glycolysis is abundant in malignancies, mitochondrial metabolism is significant as well. Mitochondria harbor the enzymes relevant for cellular respiration, which is a critical pathway for both regeneration of reduction equivalents and energy production in the form of ATP. The oxidation of NADH2 and FADH2 are fundamental since NAD and FAD are the key components of the TCA-cycle that is 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 most likely benefit from such treatments. Here, we provide a brief overview of the status quo of targeting mitochondrial energy metabolism in glioblastoma and highlight a novel combination therapy.

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Keywords - glioblastoma, metabolism, lactate, carbon tracing, central carbon metabolism

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Targeting Cellular Respiration as a Therapeutic Strategy in Glioblastoma

Mutant library

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Compared to previous variants, Omicron variant has a total of 60 mutations: 50 nonsynonymous mutations, 8 synonymous mutations, and 2 non-coding mutations. The variant has 32 mutations at the spike protein region, many of which have not been observed in other variants. The variant is characterized by 30 amino acids, three small deletions, and a small insertion in the spike protein compared to the original virus, wherein 15 is located in the receptor-binding domain. In addition, three mutations affect the Furin cleavage site, which adds SARS-CoV-2 infectivity.
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