Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance

Zhou, Weihua; Wahl, Daniel R.

doi:10.3390/cancers11091231

Cited by 93 publications

(88 citation statements)

References 210 publications

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“…Cancer-associated mutations in genes encoding IDH, FH, and SDH lead to the accumulation of 2-hydroxyglutarate, fumarate, and succinate, respectively [171][172][173]. Multiple mutations in IDH isoenzymes IDH1 and IDH2, which normally catalyze oxidative decarboxylation of isocitrate to α-KG, have been shown to occur frequently in gliomas and acute myeloid leukemia [174][175][176]. They lead to decrease in α-KG content and simultaneous increase in the amount of its antagonist, 2-hydroxyglutarate [177].…”

Section: Pdc and Tca Cyclementioning

confidence: 99%

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Moldogazieva

Mokhosoev

Terentiev

2020

Cancers

110

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It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) to glycolysis in order to meet elevated requirements in energy and nutrients for proliferation, migration, and survival. However, data accumulated over recent years has increasingly provided evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism, even in the same tumor. This phenomenon, denoted as cancer cell metabolic plasticity or hybrid metabolism, depends on a tumor micro-environment that is highly heterogeneous and influenced by an intensity of vasculature and blood flow, oxygen concentration, and nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, and reactive oxygen species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of a switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, glucose transporters (GLUTs), and AMPK with other regulatory proteins including oncogenes such as c-Myc, p53, and KRAS; growth factor-initiated protein kinase B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), and mTOR signaling pathways; and tumor suppressors such as liver kinase B1 (LKB1) and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discover novel anti-cancer drugs.

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Section: Pdc and Tca Cyclementioning

confidence: 99%

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Moldogazieva

Mokhosoev

Terentiev

2020

Cancers

110

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“…The modification of metabolism and mitochondrial bioenergetics detected in GBM cells fuels survival, proliferation, and invasion. Emerging reports suggest that metabolic alteration also mediates resistance to standard-of-care therapies in GBM [ 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]. In particular, high rates of glycolysis have been correlated with GBM radioresistance, and inhibition of the glycolytic pathway has been shown to reduce this resistance in vitro and in vivo [ 120 , 121 ].…”

Section: Mechanisms Of Gbm Radioresistancementioning

confidence: 99%

Radioresistance in Glioblastoma and the Development of Radiosensitizers

Ali

Oliva

Noman

et al. 2020

Cancers

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Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

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“…[ 87,88 ] Many studies have also proposed that GBM cells frequently acquire chemoresistance and radioresistance by exploiting their intrinsic resistance to apoptosis and by reprogramming their proliferation and survival pathways during GBM progression. [ 89,90 ] In the past few years, pulsed electric fields have also been demonstrated to be able to initiate apoptosis in GBM cells. [ 91 ] CAP treatment differs from radiation, chemotherapy, and electromagnetic fields; chemotherapy has systemic side effects, whereas electromagnetic fields are penetrating, causing injury to the surrounding tissue.…”

Section: Cap‐based Combination Therapy Strategies For Gbmmentioning

confidence: 99%

The emerging role of cold atmospheric plasma in glioblastoma therapy

Zandsalimi

Aghamiri

Roshanzamiri

et al. 2020

Plasma Processes & Polymers

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Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. In spite of substantial progress in the understanding of gliomas biology, there has been only a slight change in the treatment of these types of tumors in the past few years. Moreover, chemotherapeutic strategies for GBM are accompanied by a lack of selectivity, serious side effects, and drug resistance. Recently, the emergence of cold atmospheric plasma (CAP), a quasi-neutral highly reactive (partially) ionized gas at close to room temperature, technology has heralded a new exciting era in cancer therapy. CAP generates a unique, rich environment of reactive oxygen and nitrogen species, photons, charged ions, and an electric field, which makes it a promising robust tool for the treatment of different types of cancers. In this review, we present recent progress of CAP in the treatment of GBM. Most importantly, the combination of CAP-based therapeutic systems and other cancer therapies including chemotherapy and nanotherapy that offer great potential for GBM therapy is covered.

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Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance

Cited by 93 publications

References 210 publications

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Metabolic Heterogeneity of Cancer Cells: An Interplay between HIF-1, GLUTs, and AMPK

Radioresistance in Glioblastoma and the Development of Radiosensitizers

The emerging role of cold atmospheric plasma in glioblastoma therapy

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