Giving Hope to Families Without Options
September 8, 2020
Using precision medicine, advanced technologies can rapidly diagnose and decode each child’s disease down to the cellular level to customize treatments and maximize cure rates while minimizing side effects.
The gift of time
The families who come to see Dr. Meg Macy are out of options and out of time. Many of her patients have spent years in treatment, trying everything from surgery to chemotherapy to radiation. And still, the cancer has returned, ruthless and unrelenting.
“We’re often the end of the road for them,” says Dr. Macy, a pediatric oncologist at Children’s Hospital Colorado. “They come to us as their last hope.”
As Director of Clinical Research at the Center for Cancer and Blood Disorders, Dr. Macy has spent her career trying to outsmart the toughest pediatric cancers. She also leads the Children’s Colorado Experimental Therapeutics Program, and her team is dedicated to bringing novel treatments and early-phase clinical trials to children with particularly complex or recurring cancers that haven’t responded to standard therapies.
“We don’t always know if these new drugs will work, but these families are at the point where they are willing to take a leap of faith,” says Dr. Macy, who is the holder of the Hoover Family Endowed Chair in Cancer Research and Innovation. “We try to provide a balance of maintaining a child’s quality of life, while offering a reasonable new therapeutic option.”
Families come from all over the country to see Dr. Macy in hopes of gaining a priceless gift: more time with their child. The final outcome isn’t always a long and healthy life, but when you’re treating the very sickest of patients, you celebrate every victory, the big and the small.
“If I can help a kid to make it to graduation or get their hair back, that’s a win for me,” she says. “If I can give them two or three more years where they can do what they want to do and not feel sick? That’s huge.”
Hope in targeted therapies
Most of the drugs currently used to treat pediatric cancer were originally developed for adult cancers more than 50 years ago. These treatments, including chemotherapy and radiation, can effectively kill cancer cells, but they also wipe out the body’s “good” cells in the process. Oftentimes they cause long-term side effects, such as organ damage or infertility.
Dr. Macy wants to find better, less invasive cures. Her research focuses on an emerging treatment approach known as precision medicine. Rather than using a “one-drug-fits-all” approach, precision medicine enables doctors to analyze each patient’s genetic make-up, cancer type, tumor mutation and other factors to predict which treatment or drug combination will work best.
“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.”
Using a tissue sample, Dr. Macy and her team can run genetic sequencing tests to decode each child’s disease and cancer down to the cellular level.
“With that information, 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.
By delivering customized treatments that target cancer cells with laser-like precision, doctors can maximize cure rates while minimizing side effects. These targeted therapies aren’t yet available for all patients, but Dr. Macy is making rapid progress through her groundbreaking research on the Anschutz Medical Campus.
“We’re seeing some really promising outcomes that have resulted in therapies getting approved from early trials,” she says.
With support from Dr. Macy, Children’s Colorado participated in a multi-site clinical trial for the first-ever targeted drug for epithelioid sarcoma. In March 2020, the Food and Drug Administration (FDA) approved the drug, known as tazemetostat, which has proven highly effective at inhibiting a gene that causes tumor growth in patients with a genetic mutation known as EZH2.
Today, Dr. Macy and her team are part of another promising trial for a drug that disrupts the activity of a protein that fuels tumor growth in cancer patients with fusion genes known as NTRK.
“I’ve had several patients on the trial who’ve had an encouraging response,” 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. These drugs are working.”
The need for funding
Pediatric cancer receives a fraction of the research dollars that are invested into adult research. Because the pediatric population is smaller – and many childhood cancers are rare – pharmaceutical companies are less motivated to fund research studies for new drugs and therapies for kids.
Knowing how long it can take to get a new drug from the laboratory to patients who have no time to waste, the Experimental Therapeutics Program is blazing its own path to find better therapies for childhood cancers. But running a clinical trial requires significant infrastructure and staffing support, all of which takes funding. That makes private philanthropy vitally important to Dr. Macy’s work.
“Not only do we need support for the clinical trials, we also need funding for all the pre-clinical work that allows us to discover the targets and pathways that we need to be hitting to make our therapies more effective,” says Dr Macy.
For Dr. Macy, the only thing more exciting than advancing new therapies in the lab is to see the direct impact of the research on her patients. She recalls one patient who had a neuroblastoma tumor that wasn’t responding to surgery or chemo. The outlook was bleak. Then Dr. Macy put her on a new drug as part of an early clinical trial. The tumor finally started shrinking, and today the child is doing ballet.
“When I have a patient come in, and I get to put up a scan that shows the cancer has disappeared, there’s nothing better than that in the world,” says Dr. Macy.