Action of Signaling Pathway Surprises Researchers Investigating Brain Tumor Development

A signaling pathway present in most organisms suppresses the formation of specific types of brain tumor, according to research recently published in Cancer Cell (doi:10.1016/j.ccell.2015.10.008).

Gliomas are the most common brain tumors in adults, and the prognosis for patients with these tumors is, in many cases, poor. Therefore, novel and effective therapies for glioma treatment are needed. An understanding of the biology of this type of tumor is a vital part of developing new therapies for gliomas.

To date, which brain cells form a glioma when a gene mutation is acquired has been highly debated. However, researchers believe that brain stem cells might be a potential source of this type of cancer. Stem cells in the human brain can generate new nerve cells; if something goes wrong in this process, uncontrolled proliferation or impaired differentiation may lead to the formation of a brain tumor.

A research team led by Professor Verdon Taylor from the Department of Biomedicine at the University of Basel in Switzerland has studied whether 1 molecular mechanism that controls normal stem cell maintenance in the brain is hijacked and used by cancer cells during tumor formation.

The researchers studied the Notch pathway, a signaling pathway central to brain stem cell activity. A proposed theory is that once aberrantly activated the Notch pathway contributes to the growth of gliomas.

"In contrast to our expectations, we found that the opposite is the case: when activated, this pathway actually suppresses the formation of some types of glioma," said Claudio Giachino, PhD, also of the University of Basel and first author of the study. Conversely, the inactivation of the pathway in some forms of glioma accelerates growth, making the tumor more aggressive.

Due to these properties, the Notch pathway could not only serve as a new therapeutic target but also a diagnostic tool that generates more reliable prognoses for disease progression and patient survival.

"Our results demonstrate major differences in the molecular requirements between seemingly similar types of brain tumor and indicate that gliomas must be carefully examined before selecting potentially specific therapeutic interventions in the future," said Taylor.

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