Functional Precision Medicine Shows Promise for Kids With Tough Cancers

By Deborah Borfitz

May 9, 2024 | A cancer researcher at Florida International University (FIU) has developed a functional precision medicine (FPM) approach to oncology treatment decision-making that combines genomic profiling with drug sensitivity testing on patient-derived tumor cells. Children with relapsed or refractory cancers are among the initial beneficiaries, according to Diana Azzam, assistant professor of environmental health sciences at the FIU Robert Stempel College of Public Health and Social Work. 

The feat is made possible by advances over the last two decades in the way tumor cells are grown in the lab and the large number of drugs that have been approved by the U.S. Food and Drug Administration (FDA) to treat cancer in adults, she says. Cancer cells get enriched and processed to mimic how they would normally grow in the body, and then exposed to dozens of FDA-approved drugs, alone and in various combinations, to identify the most effective options. 

The drug screening exercise only takes about one week, so oncologists can quickly get patients started on the most promising picks, says Azzam. Genomic testing takes a bit longer and, if anything turns up that is actionable, the treatment regimen can be modified accordingly. 

A feasibility study enrolling 25 children at Nicklaus Children’s Hospital in Miami, which published recently in Nature Medicine (DOI: 10.1038/s41591-024-02848-4), demonstrated the potential for FPM to positively impact clinical care for pediatric and adolescent patients with recurrent or refractory cancer. A larger, 65-patient study has since been launched and planning is underway for further validation via a large-scale, multi-center randomized clinical trial, Azzam reports. 

Hesitation of treating physicians to use FPM data recommendations to help make informed decisions for their patients has been a significant obstacle, she notes. In the latest pediatric study, only six of the 14 patients treated followed FPM guidance and the remainder relied on the physician’s own knowledge and expertise.  

Notably, among the six patients receiving FPM-guided treatments, five (83%) experienced improved outcomes. Specifically, they had a greater than 1.3-fold improvement in progression-free survival relative to their previous therapy and demonstrated a significant increase in progression-free survival and objective response rate compared to those of the eight non-guided patients. 

“We need to work on physician awareness,” says Azzam. “Hopefully, the more data we can generate for functional precision medicine, the more physicians will adopt this approach and start working closely with cancer researchers to use these new tools to make informed decisions for their patients.” 

Azzam’s lab has received a $2 million appropriation from the State of Florida to be certified under the federal Clinical Laboratory Improvement Amendments (CLIA) Program. When the certification process is complete, likely by this summer, it will become the state’s first large-scale lab dedicated to functional cancer drug testing, she says. 

State funding was made possible by the advocacy work of the Live Like Bella Childhood Cancer Foundation, which spearheaded grassroot efforts to pass a bill supporting research projects like this on an ongoing basis, says Azzam. Thanks to the nonprofit, over $37 million has been dedicated to pediatric cancer research in Florida.  

More Options

Tumor chemosensitivity assays have traditionally been used to test a relatively small number of therapeutic agents commonly prescribed for a cancer indication to identify the best matches for an individual patient, says Azzam. But progress has been limited and the effectiveness of the tests has been under constant debate. 

Among the problems that have surfaced is that some treatments target cells present in the tumor environment that aren’t fully recapitulated in culture models, Azzam says. In her lab, patient-derived tumor cultures more faithfully represent the tumor with a mix of cell populations that include immune cells.  

Equally important, over 125 anti-cancer drugs are now FDA-approved and available for high-throughput drug testing. Given the scarcity of approved drugs for treating childhood cancers, that represents a treasure trove of potential good therapeutic options that might be considered for off-label use, which insurance companies should cover if provided evidence that they work, says Azzam. 

The prognosis for children treated for cancer is very positive only for one type of leukemia—acute lymphoblastic leukemia, where the five-year survival without relapse is about 85% and more than 90% of patients are cured of the disease. The success rate for all other pediatric cancers is not nearly that high, Azzam says. 

When standard-of-care treatments have been exhausted, physicians are often forced into cycles of trial-and-error to find effective treatments for kids with relapsed or refractory cancer, says Azzam, a board member with the Society for Functional Precision Medicine. Yet FPM tools exist to “consistently provide options for cancer patients that... are running out of options.” and turn trial-and-error into decisions based on data, evidence, and deep clinician experience. 

Her advice to parents is to remain hopeful, get in touch with a functional precision medicine researcher, and start asking questions. They have a “huge role” to play in decisions about next treatment steps. 

Scaling Up

In the FPM feasibility study, children were largely Hispanic and African American and their drug response profiles were quite different than those seen in non-minority populations, says Azzam. “This is why functional precision medicine actually can be used as a tool to reduce cancer disparities.”  

Ethnic differences were teased out using an explainable artificial intelligence (AI) platform that looks for patterns across data from drug sensitivity testing and molecular profiling as well as existing knowledge of drug interactions, she says. The model provides potential drug combinations tailored to each patient’s specific tumor characteristics, as well as uncovers potential multiomics biomarkers. 

The ongoing, 65-patient study, funded by the National Institute on Minority Health and Health Disparities, is integrating AI to start identifying biomarkers specifically expressed in minority populations that can predict patient response to cancer drugs, including targeted drugs, Azzam adds. This multi-omics biomarker AI approach was developed and is being led by Noah Berlow, chief technology officer for First Ascent Biomedical and Azzam’s colleague and collaborator. 

Test results get reported to an FPM tumor board, which meets once every two weeks to make informed treatment decisions based on each individual patient’s profile, says Azzam. The group includes translational researchers, oncologists, nurse practitioners, and clinical coordinators.  

A second FPM validation study out of Azzam’s lab is enrolling adults with all types of cancer being treated at the Cleveland Clinic.  She says she welcomes communication from physicians anywhere who are interested in helping her set up the multicenter clinical trial.  

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