Researchers identify protein pathway involved in brain tumor stem cell growth

February 26, 2015, H. Lee Moffitt Cancer Center & Research Institute

Glioblastomas are a highly aggressive type of brain tumor, with few effective treatment options. Moffitt Cancer Center researchers are one step closer to understanding glioblastoma development following the identification of a key protein signaling pathway involved in brain tumor stem cell growth and survival. Brain tumor stem cells are believed to play an important role in glioblastoma development and may be possible therapeutic targets.

The neurotrophin protein pathway controls nerve growth, survival and specialization. In an article published in the Feb. 6 issue of The Journal of Biological Chemistry, Moffitt researchers reported that the neurotrophin pathway is also involved in the survival and growth of brain tumor stem cells. The stem cells have high levels of neurotrophin receptors called TrkB and TrkC. Cellular signals from normal brain cells can activate TrkB and TrkC on the stem cells and stimulate cell growth. And when scientists inhibited TrkB and TrkC, they found decreased stem cell survival. This suggests that TrkB and TrkC may be possible drug targets for stem cells in gliomas and glioblastomas.

"This work might be a first step in developing new treatment approaches targeting brain tumor stem cells. It may also partly explain why can grow so quickly since proteins from the surrounding normal brain might be used by the tumor to grow even faster," said Peter A. Forsyth, M.D., chair of the Department of Neuro-Oncology at Moffitt.

Researchers also reported a potential reason why several clinical trials targeting a protein called EGFR in glioblastoma patients have failed to live up to expectations. EGFR is frequently activated in glioblastoma, but results from trials using EGFR inhibitors showed little or no patient improvement. Moffitt scientists discovered that TrkB and TrkC maintain brain stem cell survival and growth even when EGFR inhibitors are used. These observations suggest that one reason why EGFR inhibitors may be ineffective in glioblastoma is that TrkB and TrkC are active, thereby bypassing EGFR inhibition and allowing to continue to grow.

This is the first time that scientists have shown that TrkB and TrkC are involved in brain tumor stem . Currently, no drugs that target TrkB and TrkC have been used as brain cancer treatments. Researchers hope that these results might encourage the development of drugs that target both the stem cell compartment and the more differentiated parts of the brain tumor and result in more effective therapies.

Explore further: Glioblastoma: Study ties three genes to radiation resistance in recurrent tumors

More information: J. Biol. Chem. 2015 290: 3814-3824. DOI: 10.1074/jbc.M114.599373

Related Stories

Glioblastoma: Study ties three genes to radiation resistance in recurrent tumors

February 3, 2015
A new study identifies three genes that together enable a lethal form of brain cancer to recur and progress after radiation therapy.

Gene regulatory path revealed as target for therapy of aggressive pediatric brain cancer

February 24, 2015
Working with cells taken from children with a very rare but ferocious form of brain cancer, Johns Hopkins Kimmel Cancer Center scientists have identified a genetic pathway that acts as a master regulator of thousands of other ...

Team reveals novel way to treat drug-resistant brain tumor cells

June 1, 2012
New research from the University of Wisconsin-Madison explains why the incurable brain cancer, glioblastoma multiforme (GBM), is highly resistant to current chemotherapies.

Signaling mechanism could be target for survival, growth of tumor cells in brain cancer

December 15, 2014
UT Southwestern Medical Center neurology researchers have identified an important cell signaling mechanism that plays an important role in brain cancer and may provide a new therapeutic target.

Finding keys to glioblastoma therapeutic resistance

August 26, 2014
Researchers at the University of California, San Diego School of Medicine have found one of the keys to why certain glioblastomas – the primary form of a deadly brain cancer – are resistant to drug therapy. The answer ...

Researchers discover mechanism leading to drug resistance, metastasis in melanoma

January 12, 2015
Moffitt Cancer Center researchers have discovered a mechanism that leads to resistance to targeted therapy in melanoma patients and are investigating strategies to counteract it. Targeted biological therapy can reduce toxicity ...

Recommended for you

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

Study may explain why some triple-negative breast cancers are resistant to chemotherapy

April 19, 2018
Triple-negative breast cancer (TNBC) is an aggressive form of the disease accounting for 12 to 18 percent of breast cancers. It is a scary diagnosis, and even though chemotherapy can be effective as standard-of-care, many ...

Protein can slow intestinal tumor growth

April 19, 2018
A new mechanism for regulating stem cells in the intestine of fruit flies has been discovered by researchers at Stockholm University. In addition, it was discovered that a certain protein can slow the growth of tumours in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.