Researchers are planning a trial for individualized drug cocktails for children with a type of malignant brain tumor, using new genomic technology. Photo by skeeze/Pixabay
Aug. 30 (UPI) -- Using genomic technology, researchers are planning a clinical trial of individualized drug cocktails to treat children with a form of malignant brain tumor.
Researchers at the University of California San Francisco plan to treat up to 44 children and young adults with high-grade glioma at the UCSF Benioff Children's Hospital San Francisco and other sites in the 18-hospital Pacific Pediatric Neuro-Oncology Consortium network.
"One of the pitfalls in identifying the drugs best suited for each child is that many therapies fail to cross the blood-brain barrier or have a high enough concentration to cause a biological effect," Dr. Michael Prados, a neuro-oncologist at UCSF Benioff Children's Hospitals and founder and co-project leader of PNOC, said in a press release. "We are working with drugs that have demonstrated blood-brain barrier penetration, based upon laboratory findings or prior clinical studies. However, anticipating delivery across the blood-brain barrier is different than actually knowing its impact in an individual patient."
More than 28,000 children up to age 19 are estimated to be living with a brain tumor in the United States. The average survival rate for all primary pediatric malignant brain tumors is 73.9 percent, according to the National Brain Tumor Society.
An estimated 4,610 tumors of the brain and central nervous system are diagnosed each year in U.S. children and teens, 10 percent of which are high-grade gliomas.
Patients with high-grade glioma, including anaplastic astrocytoma, glioblastoma and midline high-grade glioma, will be tested.
"While survival for some childhood cancers has been improving since the 1970s, this has not happened for some solid tumors, including types of pediatric brain tumors," said project leader Dr. Sabine Mueller, a UCSF Health neuro-oncologist.
Surgical techniques for brain tumors have improved, but some high-grade gliomas are inoperable or cannot be totally removed, Mueller said. Also, chemotherapy and radiation may extend survival, but they often are resistant to long-term remission.
"We have learned a lot about the molecular makeup of high-grade gliomas in recent years and we recognize that their heterogeneity means that a blanket treatment approach fails to reach most patients," Mueller said. "We hope that this personalized strategy may lead the way to life-saving treatments for children with high-grade gliomas, as well as other treatment-resistant brain tumors."
In the trial, researchers will analyze tumor samples and "read" the genetic makeup of the tumor and normal cells with a DNA sequencer.
Then, genetic alterations may be matched with existing targeted therapies or investigational drugs that block the cancer development. Scientists also will check DNA sequences in healthy cells for any germline or heritable mutations that increase other cancers' risk.
Up to four therapies will be specifically targeted to the child's tumor. The UCSF 500 Cancer Gene Panel, which flags the most common cancer genetic mutations, will screen the samples. And molecular profiling and analysis services will be provided by NantHealth, Inc., a personalized healthcare company utilizing advancements in technology and precision medicine.
"By sequencing the entire genome, this technology ensures the most comprehensive and actionable data about the biology of the tumor will be available to the oncologist before treatment begins," Dr. Patrick Soon-Shiong, chairman and CEO of NantHealth. said. "The application in this study is of particular interest because there are generally fewer DNA mutations in pediatric cancers than in adult variations."
A parallel trial also is underway at UCSF Benioff Children's Hospital San Francisco and other PNOC sites for children with the most virulent high-grade glioma, known as diffuse intrinsic pontine glioma, using a similar precision medicine approach.