‘Next-Level’ Precision Medicine: CHOP Frontier Program Is Redefining Cancer Care

CHOP will become the first hospital in the United States to offer advanced genome sequencing in the operating room to diagnose brain tumors next to a patient’s bedside as part of the Advanced Personalized Therapeutics and Precision Surgery Program in Childhood Cancers Frontier Program.

A new Frontier Program at Children's Hospital of Philadelphia is transforming pediatric cancer care by tailoring medical treatment to the specific vulnerabilities in an individual's tumor, such as genes or proteins.

The Advanced Personalized Therapeutics and Precision Surgery Program in Childhood Cancers will integrate advanced molecular tumor profiling, functional tumor testing, and real-time intraoperative tumor sequencing into pediatric cancer treatment plans.

The team also is working to make CHOP the first hospital in the United States to offer advanced genome sequencing in the operating room to diagnose brain tumors next to a patient's bedside.

"This is the next level of individual precision medicine," said Adam Resnick, PhD, Director of CHOP's Center for Data-Driven Discovery in Biomedicine (D3b).

Dr. Resnick is leading the Frontier Program alongside principal investigators Theodore Laetsch, MD, a pediatric oncologist; Marilyn Li, MD, Vice Chief of the Division of Genomic Diagnostics; Phillip "Jay" Storm, MD, Chief of the Division of Neurosurgery; and Yi Xing, PhD Associate Chief Scientific Officer for Omics, Technology, and Engineering.

Taking the Next Steps in Personalized Care

The Frontier program builds upon initial research efforts from the Center for Precision Medicine for High-risk Pediatric Cancer. Researchers will continue to profile patients' tumors in-house at CHOP, identify their unique genetic vulnerabilities, and develop new therapies for those patients through clinical trials.

"What the new Frontier program brings is a new method of profiling these tumors — not only through genetic sequencing, but by actually growing tumor cells in the lab," Dr. Laetsch said, "to understand which drugs the tumors are most sensitive to or resistant against."

Those results can then be passed along to a patient's oncologist, so that they can prioritize treatments that are most likely to be effective. The aim is for drug-sensitivity testing to be available for every patient with high-risk, difficult-to-treat, or relapsed cancer.

For patients with solid tumors, researchers will create so-called "organoids" in the lab — miniature, three-dimensional models that mimic human organs. 

"The goal is to create a patient model within a clinically relevant timeline, which can be up to one or two weeks," Dr. Resnick said. "We can also freeze these models and reanimate them later, so they can have continued relevance for a patient throughout their clinical journey."

Bringing Advanced Diagnostics to the Operating Room

Advanced long-read sequencing technologies will help the Frontier team to understand the unique genetic fingerprint of patients' brain tumors in real-time. They will provide this critical information to surgeons based on methylation profiling next to a patient's bedside in the operating room.

"Long-read sequencing allows us to profile tumors very quickly, so we can give a surgeon results while they're still in the operating room with a patient," said Dr. Li, whose research focuses on the clinical application of high-throughput molecular technologies for cancer diagnosis.

For the Frontier team, this program represents a new era for personalized medicine in cancer care. Despite remarkable medical advancements over the past three decades, cancer remains the leading cause of disease-related death in children. Among the 15,000 children diagnosed with cancer in the U.S. each year, an estimated 2,000 to 3,000 have diseases that lack effective treatments, do not respond to therapy, or relapse.

"Our goal is to be able to predict and adapt to each individual patient's cancer more quickly, with greater accuracy and better, safer therapies," Dr. Laetsch said.