Researchers develop approach for identifying tumor targets when genetic drivers are unknown

January 5, 2018, Baylor College of Medicine

Ependymoma is a type of brain tumor that is resistant to chemotherapy. While genomic sequencing has provided molecular targets and resulted in precision oncology therapies for many cancers, effective targets for ependymomas have remained elusive. Dr. Stephen Mack, assistant professor of pediatrics – oncology and new faculty member at Baylor College of Medicine and Texas Children's Hospital, and colleagues have developed a framework for discovering targets in ependymomas, and other cancer that lack known genetic drivers, thereby also providing insights into treatment strategies. The study appears in Nature.

"Ependymoma is the third most common cancer type in children, and there are no current targeted therapies available. Even with surgery and radiation, the more aggressive tumors will keep coming back," said Mack. "Traditional genomic sequencing revealed that these tumors are relatively silent, meaning mutations in the DNA are few. However, we found changes in the way the DNA is folded and packed and how the genes are regulated."

The research team developed a more in depth approach to find the actively transcribed genes that play a role in formation, as opposed to identifying mutations alone. A specific process in the tumor's epigenome, called histone acetylation, tells genes to turn on or off, thereby regulating the action of the DNA. The team assayed the markers for this process in the ependymoma tumor type and found that the are highly active in tumor development.

"This is an important strategy to develop because we are looking at gene regulation specifically as a new approach to targeted therapy for cancers in which there are no known ," said Mack. "It can act as a complimentary tool to to identify potential targets, and could later be useful in developing drug treatment plans."

"As a neurosurgeon, it is very frustrating to operate on babies with , and then not have any effective chemotherapy. This new approach to finding effective chemotherapies discovered by Dr. Mack offers a new way forward in this very difficult disease that affects the youngest members of our society," said Dr. Michael Taylor, neurosurgeon and senior scientist in the Program in Stem Cell and Developmental Biology at the Hospital for Sick Children in Toronto.

Explore further: Molecular super enhancers: A new key for targeted therapy of brain cancer in children

More information: Stephen C. Mack et al. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling, Nature (2017). DOI: 10.1038/nature25169

Related Stories

Molecular super enhancers: A new key for targeted therapy of brain cancer in children

December 20, 2017
Ependymoma refers to a heterogeneous group of cancers that can occur at any age, and is one of the most common types of brain cancer in children. The genetic causes for its development are largely unknown and there are no ...

Brain tumors found to have a two-tier system

August 23, 2011
Ependymomas are the second most frequent type of malignant brain tumor in children. Ependymoma develops from precursor cells of the tissue that lines the hollow cavities of the brain. Therapy results of ependymoma vary immensely: ...

Comprehensive genomic analysis offers insights into causes of Wilms tumor development

August 21, 2017
A comprehensive genomic analysis of Wilms tumor - the most common kidney cancer in children - found genetic mutations involving a large number of genes that fall into two major categories. These categories involve cellular ...

New study shows that genomic profiling can help improve treatment of brain tumors in children

September 14, 2017
The largest genomic profiling study ever conducted into a type of brain tumor known as glioma in children has identified genetic alterations in 96% of cases. As reported in The Oncologist, this genetic information could help ...

Genetic testing for childhood cancer patients can identify cause and treatment potential

January 28, 2016
Combined whole exome tumor and blood sequencing in pediatric cancer patients revealed mutations that could help explain the cause of cancer or have the potential to impact clinical cancer care in 40 percent of patients in ...

Comprehensive sequencing program shows promise of precision medicine for advanced cancer

August 2, 2017
The average metastatic cancer has more genetic mutations than are seen in early stage tumors, a new study finds.

Recommended for you

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.

Area surrounding a tumor impacts how breast cancer cells grow

March 14, 2018
Cancer is typically thought of as a tumor that needs to be removed or an area that needs to be treated with radiation or chemotherapy. As a physicist and cancer researcher, Joe Gray, Ph.D., thinks differently.


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.