In her decades of treating and researching childhood cancers, University of Colorado Cancer Center leader Lia Gore, MD, has seen a lot change for the better.
In a recent article published in the journal Cell, Gore and fellow CU Cancer Center member Maureen O’Brien, MD, MS, chart 50 years of progress toward curing childhood cancer, crediting advances in genomics, immunology, surgical techniques, radiation therapy, and supportive care for helping to turn the tide.
“Fifty years ago, cancer in children was not really curable,” says Gore, co-director of the Developmental Therapeutics Program at the CU Cancer Center. “There were a small number of patients who had a realistic chance of surviving. Today, the majority of kids diagnosed with cancer are cured. What is most meaningful to me is that there are children alive today who wouldn't be otherwise. We know there are children and young adults who have gone through therapy and are on the successful side of being cured and are going on to lead exciting, productive, happy lives.”
Gore and her colleagues were on the front lines of a recent breakthrough in a specific childhood blood cancercalled B-acute lymphoblastic leukemia, co-leading the first clinical trial of an immunotherapy drug called blinatumomab that ultimately was shown to reduce relapse and improve overall survival. Part of a class of drugs called bispecific T-cell engagers (BiTEs), blinatumomab works by directing the immune system to kill cancer cells, Gore says.
“Bispecifics are essentially linkers with antibodies on each end,” she says. “One end links to a protein on the surface of an individual’s T cells, and the other end links to a protein or another characteristic on a cancer cell. It brings a cancer cell in close proximity to a patient’s T cells, which then do what they were born to do: go out and kill foreign invaders.”
In another recent article, this one for the journal Haematologica, Gore and Kaylyn Lyons, MD, a recently graduated pediatric hematology/oncology fellow at CU, reviewed some of the recent studies on BiTEs, noting that blinatumomab has induced remission in approximately 40% of the 10% to 15% of B-acute lymphoblastic leukemia patients who relapse after treatment, with a significant reduction in serious side effects. Though originally prescribed only for patients who relapsed after other treatments, blinatumomab is now being used as a frontline therapy for some children with the disease.
“There have been other immunotherapy options for these patients, but this was a completely new approach,” says Gore, who holds the Ergen Family Chair in Pediatric Oncology at Children’s Hospital Colorado. “We think of it as a living drug, because it is engaging the body's immune system in a different way from previous antibody therapies. It has allowed patients who previously did not have hope for survival to survive.”
Gore says BiTEs work in a similar way to CAR T cell therapy — in which a patient’s blood is drawn then sent to a lab, where it is re-engineered to fight cancer cells — but with BiTEs, “We can pull it off the shelf and treat somebody tomorrow,” she says.
Both BiTEs and CAR T cells have advantages and disadvantages, she says, and both are key in the immunotherapy revolution.
Despite all the advances in treating pediatric cancer, including BiTEs, Gore says there is still much work to be done. Though overall survival for childhood cancer is now at 85%, with dramatic decline in mortality rates over the past 50 years, “there are some patients for whom we haven’t made much progress,” she says. “Too many children still die of cancer, and some cancers have no better prognosis today than they did in the 1970s. Improving outcomes for the last 15% of patients is the next frontier.”
Among the strategies researchers can use to close the gap, she and O’Brien suggest, are coordinated research efforts on an international scale with pharmaceutical and biotech partners and regulatory agencies, advanced bioinformatic analyses, integration of tumor and host genomics, understanding pharmacogenomics and the tumor microenvironment, and comprehensive approaches to cost containment and access to care.
“We're going to always look for better answers,” she says. “Our next challenge is going to be improving the quality of survivorship, because we know that survivorship comes at a cost for many patients. How can we lessen those more severe and longer-term side effects? If you're treated for childhood leukemia when you're 3 or 4 years old, then my goal is that you have 85 more years of life. So, what does that 85 years look like? What are the benchmarks we have to focus on, and how can we move the needle for those patients and their families?”
She and her colleagues won’t rest, Gore says, until the research isn’t needed anymore.
“It’s a privilege to take care of children and families who entrust us with their lives,” she says. “None of us is ever going to be happy until we're unemployed because there's no need for us anymore.”