NADP+-dependent IDH1R132 mutation and its relevance for glioma patient survival

Tewarie, Nishita M.S. Baldewpersad; Burgers, Ilsa A.V.; Dawood, Yousif; Boon, Hannah; Brok, Melina G.H.E. den; Klunder, Jet H; Koopmans, Kristijn B.; Rademaker, Emma; Broek, Hans B. van den; Bersselaar, Sil M. van den; Witjes, Julia J.; Noorden, C. J. F. Van; Atai, Nadia A.

doi:10.1016/j.mehy.2013.02.022

Cited by 26 publications

(13 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, multiplex assays likely will provide information about downstream pathways as well as resistance mechanisms in glial tumors. MGMT promoter methylation status has been observed to be a predictor of glioma resistance to chemotherapy [94]. The expression of IDH1/2 mutant proteins has also been shown to sensitize GBM cells to ionizing radiation-induced apoptosis improving overall survival of these patients [93, 94].…”

Section: Discussionmentioning

confidence: 99%

Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science

Hochberg

Atai

Gonda

et al. 2014

Expert Review of Molecular Diagnostics

View full text Add to dashboard Cite

Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treatment includes surgical resection, irradiation with adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the survival of patients remains poor. There is a critical need for minimally invasive biomarkers for diagnosis and as measures of response to therapeutic interventions. Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers. In this review, we discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation.

show abstract

Section: Discussionmentioning

confidence: 99%

Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science

Hochberg

Atai

Gonda

et al. 2014

Expert Review of Molecular Diagnostics

View full text Add to dashboard Cite

show abstract

“…IDH1 activity is responsible for two thirds of the NADPH production capacity in normal brain, whereas the IDH1 mutation reduces this capacity by almost 40 %. Therefore, the reduced NADPH production capacity due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and chemotherapy, thus prolonging survival of the patients [ 83 ]. Metabolomics can be performed on a variety of clinical samples, and as a biomarker in oncology, can be used in cancer diagnosis, assessment of response to traditional therapy and development of novel therapies.…”

Section: Metabolomics In Gbmmentioning

confidence: 99%

Preclinical Models of Glioblastoma in Radiobiology: Evolving Protocols and Research Methods

Tandle

Shankavaram

Schlaff

et al. 2016

Current Clinical Pathology

View full text Add to dashboard Cite

“…Thus, IDH1 mutation limit the reduction of the ROS generated by radio-chemotherapies therefore sensitizing glioma cells to current standard of care and prolonging survival (Fig. 3 ) [ 82 ]. Noteworthy, in AML, Glucose-6-phosphate Dehydrogenase (G6PDH) is the predominant NADPH generator, not IDH.…”

Section: Pro-survival Effects Of Idh Mutationmentioning

confidence: 99%

Isocitrate Dehydrogenase (IDH) Mutation in Gliomas

Chesnelong

2015

Next Generation Sequencing in Cancer Research, Volume 2

View full text Add to dashboard Cite

First identifi ed in 2006 in a colorectal cancer sequencing effort, Isocitrate Dehydrogenase (IDH) mutations were later reported in secondary glioblastomas by Parsons et al. leading the way for further studies which have revealed the presence of mutations in either IDH1 or IDH2 in over 70 % of grade II-III gliomas and secondary glioblastomas. In the clinic, IDH1 and IDH2 mutations are important prognostic factors associated with prolonged survival and enhanced radio-and chemo-sensitivity. At the benchside, IDH mutations are a major focus of glioma research. Signifi cant progresses have been made elucidating the roles of IDH mutations in tumorigenesis. IDH mutations were shown to confer a neomorphic enzymatic activity: the reduction of α-Ketoglutarate (αKG) to 2-hydroxyglutarate (2HG). 2HG was further shown to be the main mediator of the oncogenic effects of IDH mutation leading to epigenetic alterations, extracellular matrix remodeling, and hypoxia-inducible factor 1α (HIF1a) degradation. However, many aspects remain unclear such as the potential infl uence of IDH mutations on cancer cell metabolism and whether IDH mutations, despite increasingly well-characterized oncogenic mechanisms, may also trigger pro-survival effects. Elucidating the roles of mutant IDH enzymes in tumorigenesis will signifi cantly improve our understanding of glioma biology and will lead to novel therapeutic strategies that should aim to disrupt the oncogenic properties of IDH mutations while promoting properties that may contribute to the slower growth, enhanced sensitivity to conventional therapies and overall longer survival characteristic of IDH mutant gliomas.

show abstract

NADP+-dependent IDH1R132 mutation and its relevance for glioma patient survival

Cited by 26 publications

References 51 publications

Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science

Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science

Preclinical Models of Glioblastoma in Radiobiology: Evolving Protocols and Research Methods

Isocitrate Dehydrogenase (IDH) Mutation in Gliomas

Contact Info

Product

Resources

About