Article

A Vision for Precision

December 28, 2021

How Children’s Hospital Colorado is using Genomics to transform care for kids.

It’s been 20 years since scientists with the Human Genome Project completed their groundbreaking work to map out the complex code behind human life. It took an international team of researchers 10 years and nearly $3 billion dollars to identify and catalogue the unique variations encoded in human DNA, but their findings would forever change the future of medical research.

Today, that same genetic mapping can be completed in under 48 hours. With a better understanding of the human genome and the driving forces behind an individual’s genetic variations, a new approach to health care has evolved — known as precision medicine — and it’s changing the way patients are diagnosed and treated at Children’s Hospital Colorado and health care institutions worldwide.

“The pace of discovery has really escalated in the past decade,” says Alisa Gaskell, PhD, Scientific Director of Precision Medicine at Children’s Colorado. “We now have the ability to scan the full genome with the most advanced technologies, and then use that information to inform health care decisions in a patient-centered manner. That’s a significant shift from the traditional disease- or symptom-centric approach.”

Dr. Alisa Gaskell
Dr. Alisa Gaskell, Scientific Director of Precision Medicine at Children’s Colorado

By capturing the immense data available within a person’s genome and leveraging decades of accumulated knowledge, not only can scientists identify the hundreds of thousands of gene variations present within every individual, but they are also better equipped to distinguish harmless gene alterations from rare, disease-causing ones — all in a matter of days versus months. This has become a gamechanger, especially for time-critical cases in which quick intervention can make all the difference.

An intelligently designed precision medicine program can transform the current health care paradigm. By leveraging information on a patient’s disease-driving genetic variants, doctors could direct a family to the right clinical trial or recommend the best-possible drug combination to optimize health outcomes.

“Genomic medicine offers the promise of more precise solutions,” Dr. Gaskell says. “This could mean a future in which every child’s treatment is uniquely tailored to ensure maximum efficacy and minimal side effects.”

Genomics within reach

For years, the incredible costs of DNA sequencing limited the potential of this groundbreaking technology to theoretical applications. But thanks to research being pioneered at Children’s Colorado and other pediatric medical institutions, that’s beginning to change.

In recent years, revolutionary improvements in sequencing technologies have reduced the cost of genomic testing from billions of dollars for the first draft of the genome to less than a thousand dollars. These advances are primarily driven by the accessibility of Next Generation Sequencing (NGS) — a modern DNA sequencing technology used to decode the genome in a more cost-effective and efficient manner.

“With NGS, we’re now able to cast the net wider and evaluate more of the patient’s genome to diagnose previously undiagnosable conditions,” says Scott Demarest, MD, Clinical Director of Precision Medicine at Children’s Colorado. “Families who have spent tens of thousands of dollars and years seeking answers — modern genomics can now provide an accurate diagnosis in a matter of days.”

Although pediatric genomics is still in its infancy, children’s hospitals nationwide are already investing significant resources in developing their precision medicine capabilities. Children’s Colorado launched its own precision medicine program in 2020 to bring genomic mapping within reach of everyday clinical applications and care decisions. Today, with the support of donors, Children’s Colorado is broadening the use of genomics to diagnose children faster, treat them more effectively and — in remarkable cases — develop individually tailored cures that could mitigate the effects of a genetic disease.

“Philanthropy has been instrumental in expanding our precision medicine program to help more patients,” says Gregor Stoddard, Director of Precision Medicine at Children’s Colorado. “Donors are now helping us to take this knowledge and technology to the next level to transform the everyday practice of pediatric medicine.”

Hope in Targeted Cancer Therapies

Pediatric oncology is one of the most promising areas of precision medicine discovery at Children’s Colorado, where doctors are using genomics to deliver customized treatments that target malignant cells with laser-like precision. Most of the drugs currently used to treat pediatric cancers were originally developed for adult cancers more than 50 years ago. These treatments, including chemotherapy and radiation, can effectively kill most types of cancer, but they also wipe out the body’s “good” cells in the process and can cause long-term side effects.

As Director of Clinical Research at the Children’s Colorado Center for Cancer and Blood Disorders, Dr. Meg Macy, Hoover Family Endowed Chair for Cancer Research and Innovation, has dedicated her career to pediatric oncology research. She also leads the Experimental Therapeutics Program, which utilizes genetic sequencing to develop novel treatments for children with complex or recurring cancers.

“With precision medicine, we’re taking a targeted approach,” explains Dr. Macy. “It’s studying each patient’s cancer cells and finding the weakness. If I can find a therapy that’s less toxic but more effective, then we can improve survival rates without all the side effects.”

Rather than using a “one-drug-fits-all” approach, Dr. Macy’s lab uses information about the patient’s unique genetic makeup, cancer type, tumor mutation and other factors to predict which treatment or drug combination will work best.

“We can try to see if there’s a gene that’s making the cancer cells grow that we can turn off. Or we can try to make the chemo more effective by targeting a specific pathway that’s enabling the cancer cells to survive,” says Dr. Macy. “We’re seeing some real wins, because we’re figuring out these molecular fusions and mutations, and we can actually target them.”

Dr. Meg Macy with Myers, one of her patients

A new paradigm

A successful precision medicine program requires a new paradigm — not to mention the right tools, technologies and team. Through focused investments in genomics and precision medicine, donors can help build a new system of care at Children’s Colorado — one that catalyzes extraordinary discoveries that improve the health of children everywhere.

“We have a vision to build a unique precision medicine program that revolutionizes the way we care for children,” Dr. Demarest says. “There has never been a more exciting time to be in medicine.”

Children’s Colorado has already begun to strategically build the underlying infrastructure and systems needed to leverage its precision medicine expertise, while maximizing synergies between its research and clinical programs. In the coming years, Children’s Colorado plans to augment its modeling, profiling, and data analysis capabilities to translate sequencing results into real-time decisions and discoveries.

“To have a robust dataset is not enough,” Dr. Demarest explains. “We must be able to use our sequencing data to improve care and advance more effective treatments as quickly as possible.”

Enhanced data profiling means that physicians can view — in real time — how other patients with similar genetic profiles and tumors have responded to different treatments. It also means Children’s Colorado can analyze the unique factors that cause therapies to be toxic or effective, nimbly adjust treatments as needed and proactively establish contingency plans — all based on a patient’s genetic profile.

Armed with the precious information provided by genetic testing, researchers can also design better clinical trials, while ensuring patients are being directed to the right trials to maximize their chances of success. Investments in these smarter, more precise research projects and trials will accelerate the discovery and deployment of novel therapies for patients worldwide.

Pediatric medical research is significantly underfunded nationwide, so donors are the driving force behind this new state-of-the-art system for enhanced sequencing and results. With the support of generous philanthropists, Children’s Colorado plans to begin rolling out faster, more cost-effective genomic testing as the standard of care for all oncology patients — and eventually to patients across all hospital service lines.

“By integrating genomic medicine into the care of children, we can give the right kids the right treatments,” Dr. Demarest says. “Ultimately, this means better outcomes, higher survival rates and greater hope for families.”