Using Mathematics to Treat Brain Tumors
August 15, 2017
Nearly one in every five children with NF1 will develop a brain tumor involving the nerve that carries vision from the eye to the brain (optic nerve). When these tumors begin to affect vision, the decision to start chemotherapy is made. Unfortunately, despite treatment, many of these optic gliomas do not stop growing or vision continues to worsen. In an effort to identify more effective therapies, advanced mathematic approaches were applied to whole tumor RNA sequencing data.
Yuan Pan, PhD, a postdoctoral research scientist in the laboratory of Dr. David Gutmann, working with Dr. Peter Sims at Columbia University, identified a group of 25 genes that distinguish optic glioma from normal optic nerve. For these studies, they employed several different mouse models of Nf1 optic glioma, and showed that this core set of genes was also found in human tumors.
Next, they asked how conventional and new experimental therapies affect this core gene signature. They were specifically looking for treatments that would result in loss of expression of these tumor-related genes, making the tumors more closely resemble the normal optic nerve. While all treatments caused the mouse optic gliomas to shrink, only one therapy caused normalization of the 25-core signature.
Surprising, neither carboplatin, a first-line treatment for children with NF1-optic glioma, nor rapamycin, an investigational drug that recently was evaluated in clinical trials, successfully normalized this signature. The treatment showing the most robust effect used a drug that impairs the function of immune system-like cells in the brain, called microglia, suggesting that targeting these cells may be a promising approach.
Future studies are planned to use this mathematic method to better predict treatment responses.
This work appears in the journal Oncotarget.
Pan Y, Bush EC, Toonen JA, Ma Y, Solga AC, Sims PA, Gutmann DH. Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature. Oncotarget. 2017 Apr 18. doi: 10.18632/oncotarget.17193. [Epub ahead of print]Categories: