By: Bhawana Jain

Published on: January 25, 2017

Article Source: UT Southwestern Medical Center

Abstract:

Scientists have identified a way to inhibit the growth of glioblastoma, a type of brain cancer which cause low survival rates in patients, by targeting a protein which contributes to the growth of brain tumors, according to research.

Complete article:

Glioblastoma, a type of brain cancer with low survival rate, gets the highest number of cases of all malignant tumors. According to the latest statistics, there will be estimated 12,290 new cases of this fatal disease in 2017. It represents 14.9% of all primary brain tumors while 55.4% of all gliomas.  Scientists from the Peter O’Donnell Jr. Brain Institute and Harold C. Simmons Comprehensive Cancer Center have found a new way to inhibit its growth by targeting a protein which causes the growth of brain tumors.

In the context of this research, the study’s co-senior author Dr. Robert Bachoo, Associate Professor of Neurology and Neurotherapeutics, Internal Medicine said, “these findings change our fundamental understanding of the molecular basis of glioblastoma, and how to treat it.”

For the past decade, patients diagnosed with glioblastoma have been treated through surgery followed by chemotherapy and radiation. This procedure has a limited advantage as it only improves median survival by an average of four to six months, followed by recurrence of the tumor. So far, there is no successful therapy to treat glioblastoma patients when the tumor recurs. Five-year survival rates are around 5 percent. This is the reason, the scientists made an attempt for genetic studies to guide possible treatment strategies.

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“Our work shows that the gene mutations which the pharmaceutical industry and clinicians have been focusing on are essential only for starting tumor growth. Once the tumor has advanced to the stage where patients seek treatment, these mutations are no longer required for continued tumor growth; they are in effect redundant,” says Dr. Bachoo, a member of the Simmons Cancer Center and O’Donnell Brain Institute. Previously, proteins called receptor tyrosine kinase were considered the drivers of glioblastoma; however, drugs that inhibit these proteins have not been effective in treating this type of cancer.

“We learned that, instead, it is neurodevelopmental transcription factors (master proteins that regulate the activity of hundreds of genes during normal brain development), which are reactivated to drive the growth of glioblastoma. We can inhibit these transcription factors and prevent further tumor growth with the chemotherapy drug mithramycin, a drug that has not been in clinical use for years due to its side effects,” says co-senior author Dr. Ralf Kittler, Assistant Professor of Pharmacology in the Eugene McDermott Center for Human Growth and Development. “Our discovery has the potential for the development of a new therapy that may increase survival time for glioblastoma patients.”

The study represents research from UT Southwestern’s precision medicine campaign in neuro-oncology and has been published in the journal Cell Reports.

Journal Reference:

Dinesh K. Singh et al. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives GlioblastomaCell Reports, January 2017 DOI: 10.1016/j.celrep.2016.12.064