ArticlePathology oncology research : POR2020
Inhibition of Metabolic Shift can Decrease Therapy Resistance in Human High-Grade Glioma Cells.
Article in Pathology oncology research : POR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- A systematic review on the potential of modulating the IRE arm of the UPR in U87 and U251 glioblastoma cells for improved therapeutic efficacy.Molecular biology research communications · 2026Review
- Review
- Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways.Scientific reports · 2024Article
- mTOR hyperactivity andPathology oncology research : POR · 2024Review
- Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.Scientific reports · 2023Article
- Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics.International journal of molecular sciences · 2022Article
- Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting.International journal of molecular sciences · 2022Article
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- Rapamycin Plus Doxycycline Combination Affects Growth Arrest and Selective Autophagy-Dependent Cell Death in Breast Cancer Cells.International journal of molecular sciences · 2021Article
- GliPR1 knockdown by RNA interference exerts anti-glioma effects in vitro and in vivo.Journal of neuro-oncology · 2021Article
- Hypoxia Signaling in Cancer: From Basics to Clinical Practice.Pathology oncology research : POR · 2021Review
- Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas.Journal of molecular medicine (Berlin, Germany) · 2020Review
- In Situ Metabolic Characterisation of Breast Cancer and Its Potential Impact on Therapy.Cancers · 2020Article
- Oxidative Stress-Part of the Solution or Part of the Problem in the Hypoxic Environment of a Brain Tumor.Antioxidants (Basel, Switzerland) · 2020Article
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tumours in central nervous system. The developing resistance against recent therapies and the recurrence rate of GBMs are extremely high. In spite several new ongoing trials, GBM therapies could not significantly increase the survival rate of the patients as significantly. The presence of inter- and intra-tumoral heterogeneity of GBMs arise the problem to find both the pre-existing potential resistant clones and the cellular processes which promote the adaptation mechanisms such as multidrug resistance, stem cell-ness or metabolic alterations, etc. In our work, the in situ metabolic heterogeneity of high-grade human glioblastoma cases were analysed by immunohistochemistry using tissue-microarray. The potential importance of the detected metabolic heterogeneity was tested in three glioma cell lines (grade III-IV) using protein expression analyses (Western blot and WES Simple) and therapeutic drug (temozolomide), metabolic inhibitor treatments (including glutaminase inhibitor) to compare the effects of rapamycin (RAPA) and glutaminase inhibitor combinations in vitro (Alamar Blue and SRB tests). The importance of individual differences and metabolic alterations were observed in mono-therapeutic failures, especially the enhanced Rictor expressions after different mono-treatments in correlation to lower sensitivity (temozolomide, doxycycline, etomoxir, BPTES). RAPA combinations with other metabolic inhibitors were the best strategies except for RAPA+glutaminase inhibitor. These observations underline the importance of multi-targeting metabolic pathways. Finally, our data suggest that the detected metabolic heterogeneity (the high mTORC2 complex activity, enhanced expression of Rictor, p-Akt, p-S6, CPT1A, and LDHA enzymes in glioma cases) and the microenvironmental or treatment induced metabolic shift can be potential targets in combination therapy. Therefore, it should be considered to map tissue heterogeneity and alterations with several cellular metabolism markers in biopsy materials after applying recently available or new treatments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.