Metabolic drivers in aggressive brain tumors
Reporter: Prabodh Kandala, PhD
Delineation of metabolic pathways are leading to novel insights into the way cancer cells behave. A recent study demonstrated the metabolic programs that drive glioblastoma, most aggressive form of glioma. Dr. Prakash Chinnaiyan’s group from Moffitt Cancer Center identified metabolic signatures that may pave a way for personalized therapy in glioma. They presented their findings in Cancer Research, the premier journal of American Association of Cancer Research.
This study used metabolomics, which is the global quantitative assessment of metabolites within a biological system, to identify some of the central metabolic pathways that allow for these tumors to grow. These findings provide a unique insight into the underlying biology of glioma and appear to have prognostic significance.
These studies conducted global metabolomic profiling on patient-derived glioma specimens and identified specific metabolic programs differentiating low- and high-grade tumors, with the metabolic signature of glioblastoma reflecting accelerated anabolic metabolism. When coupled with transcriptional profiles, Dr. Chinnaiyan’s group identified the metabolic phenotype of the mesenchymal subtype to consist of accumulation of the glycolytic intermediate phosphoenolpyruvate and decreased pyruvate kinase activity. Unbiased hierarchical clustering of metabolomic profiles identified three subclasses, which they termed energetic, anabolic, and phospholipid catabolism with prognostic relevance. These studies represent the first global metabolomic profiling of glioma, offering a previously undescribed window into their metabolic heterogeneity, and provide the requisite framework for strategies designed to target metabolism in this rapidly fatal malignancy.
Ref:
1. H. Lee Moffitt Cancer Center & Research Institute. “Novel metabolic programs found driving aggressive brain tumors.” ScienceDaily, 9 Nov. 2012. Web. 11 Nov. 2012.
2. P. Chinnaiyan, E. Kensicki, G. Bloom, A. Prabhu, B. Sarcar, S. Kahali, S. Eschrich, X. Qu, P. Forsyth, R. Gillies. The Metabolomic Signature of Malignant Glioma Reflects Accelerated Anabolic Metabolism. Cancer Research, 2012; DOI: 10.1158/0008-5472.CAN-12-1572-T
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I would want to know how this classification is in agreement with the pathology. I don’t think patients with Glioblastoma multiforme, the most agressive, live beyond a year. This malignancy also has a very anaplastic look and is vascular. Grades I and II have a less agressive course, but they also don’t live that long. Ultimately you are faced with intracranial compression and the brain stem is pushed down into the spinal canal.
I had a good friend die of it, and another friend had a family member die with it.
Dear Larry,
I agree with you. Glioma is too aggressive cancer for patients to survive more than an year. I followed one of my colleagues while working on few in vivo models for gliomas and they hardly used to survive week or two after tumor implantation.
However, this study is the first step to demonstrate the metabolic aspects in glioma. I believe a lot more has to be done to answer your question.
Especially in vivo studies and live imaging might help to know us better.
And importantly, Metabolism in cancer is gaining importance and more work is performed in vitro compared to in vivo. More answers to come in the future.
Dr Larry showed the reality of today……..I treat patients with this very letal malignancy.But DR Kandala shared with us a very importante window!A new way hope in the future.Congratulations!
Dr. Prabodth,
Thank you for this post.
I would like to see graphical presentation, alternative treatment methods, an opening paragraph on research trends in metabolomics, situation of glioma in this context.
We have a research category: Metabolomics, please check it off.
I noted you connected the post to Cancer Research LinkedIn Group, pl.do so with our own Group and all othe Groups, is your membership 50 Groups?
You need to get hits on every post on cancer to make it into the forthcoming e-Book on cancer, you are one of four Editors of.
Please be inspired by other EAW regarding the depth of the thematic theme discussion in a post. In open access online Scientific Journal the burden on the reader should be minimal. No reader should go to start a research on the theme presenter because the post was too siscinct or touched a thin veneer, only.
Graphics and media integration are highly encouraged.
Dr. Probodh, was the initial metabolic analysis blinded with respect to stage of tumors? Or did the study authors select a cohort of high/low grade patients which, I am assuming pathology was performed. I am interested in this finding of decreased pyruvate kinase and increased PEP and wonder if the more aggressive gliobastomas have altered metabolism which support anaerobic metabolism (as Dr. Berstein had described in his previous posts on Warburg effect and cancer)? In addition, Dr. Kandala, are the in vivo models only s.c. xenografts or are there GEM models of glioblastoma multiforme?
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I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette