The 3rd biennial Pediatric Neuro-Oncology Basic and Translational Research Conference jointly sponsored by the Society of Neuro-Oncology and the Children's Brain Tumor Foundation will be held on May 16th and 17th in Fort Lauderdale Florida. Several of the already available abstracts are several on DIPG. One of the ones that caught my eye will be a poster presentation from Australian researchers entitled " Targeting mitochondria and metabolism as a novel therapeutic approach in the treatment of Diffuse Intrinsic Pontine Glioma".
The interest in cellular metabolism in cancer goes back the early 1900's with Otto Heinrich Warburg. The Warburg Hypothesis says "the prime cause of cancer is the replacement of the respiratory of oxygen in normal body cells by a fermentation of sugar." He speculated that tumor development is driven by insults to the mitochondria which affects cellular respiration. Mitochondria have become a potential target for cancer therapy. One of the key mitochondrial proteins implicated in cancer has been adenine nucleotide translocase (ANT).
In this abstract, the researchers used DIPG neurospheres to evaluate the effectiveness of an ANT inhibitor PENAO. This agent appears to have first hit the internet in 2011, when some of the authors unveiled this novel compound at AACR in an abstract " PENAO: A small molecule tumor metabolism inhibitor". In the AACR abstract PENAO led arrest of proliferation and apoptosis of tumors cells. It was well tolerated by IV and subcutaneously in mice.
In this study, the use of PENAO on DIPG neurospheres was found to be a "promising therapeutic strategy" to treat DIPG. In addition, combination with a MRP1 ( multidrug resistance-associated protein ), Reversan, increased the effect. Effectiveness of PENAO was also increased by 3-bromopyruvate.
This is interesting research with a different approach to DIPG in utilizing mitochondrial small molecule inhibitors. Now, the challenge would seem to be in the steps to translate this from bench to bedside. The great thing now compared to just a few years ago is that several institutions have been able to developed DIPG animal models to be able to preform the necessary translational research.
Reference:
Targeting mitochondria and metabolism as a novel therapeutic approach in the treatment of Diffuse Intrinsic Pontine Glioma
https://soc-neuro-onc.conference-services.net/reports/template/onetextabstract.xml?xsl=template/onetextabstract.xsl&conferenceID=3467&abstractID=740145
Mitochondria and Cancer: Past, Present, and Future
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581248/
Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer
http://www.ncbi.nlm.nih.gov/pubmed/20950584
Inhibition of Glycolysis in Cancer Cells: A Novel Strategy to Overcome Drug Resistance Associated with Mitochondrial Respiratory Defect and Hypoxia
http://cancerres.aacrjournals.org/content/65/2/613.full
