Functional Precision Medicine Method Aids Treatment Decision-Making in R/R Pediatric Cancers


A unique approach combining genomic and sensitivity testing with machine learning was feasible for guiding treatment selection in pediatric cancers.

Diana Azzam, PhD

Diana Azzam, PhD

A functional precision medicine approach that combines genomic testing with drug sensitivity testing was feasible when used to inform treatment decisions for pediatric patients with difficult-to-treat, relapsed/refractory solid and hematologic malignancies, according to findings from an observational study (NCT03860376) published in Nature Medicine.1,2

Findings from the proof-of-concept study demonstrated that 83% of patients who received functional precision medicine–guided treatments (n = 6) experienced an improvement in progression-free survival (PFS) greater than 1.3-fold relative to their previous treatment. The PFS in the investigational cohort was significantly longer compared with matched previous regimens (P = .0001) and the physician’s choice of treatment cohort (P = .0037). Additionally, 83% of patients achieved an objective response in the functional precision medicine-guided cohort compared with 13% in the physician’s choice of treatment cohort (n = 8).2

"The results are exciting because cancer that comes back is much harder to treat,” Diana Azzam, PhD, an assistant professor and research director of the Center for Advancing Personalized Cancer Treatments (CAPCT) at Florida International University in Miami, as well as the study’s lead author, said in a press release. “Seeing improvement in 83 percent of patients is incredibly promising. This could be the way we turn cancer into a manageable disease."1

The functional precision medicine approach involved the collection of fresh primary tumor samples from each patient, which were then analyzed using a combination of drug sensitivity testing assays, genomic panel sequencing, immunofluorescence, and machine learning. The study enrolled patients aged 21 years or younger with a suspected or confirmed diagnosis of recurrent or refractory cancer who had exhausted standard-of-care (SOC) treatment options. These patients were scheduled for or had recently undergone biopsy or tumor excision or bone marrow aspiration.2

The primary objective of the study was to determine the feasibility of returning functional precision medicine-based treatment recommendations in real time to the functional precision medicine tumor board within a clinically actionable timeframe of 4 weeks or less. The secondary objective was to compare clinical outcomes in enrolled patients who underwent functional precision medicine–guided treatment with those of patients who previously received treatments and those of patients who received physician’s choice of treatment.

At baseline, the overall study population (n = 25) was a median age of 10 years old (range, 0.81-21) and underwent a median of 3 (range, 2-6) prior lines of therapy. Most patients were female (60%) and White (84%). The study included patients with acute lymphoblastic leukemia (n = 3), acute myeloid leukemia (n = 3), astrocytoma (n = 1), ependymoma (n = 1), Ewing sarcoma (n = 4), glioblastoma multiforme (n = 1), medulloblastoma (n = 1), malignant rhabdoid tumor (n = 1), neuroblastoma (n = 1), osteosarcoma (n = 4), rhabdomyosarcoma (n = 4), and Wilms tumor (n = 1).

Twenty-one patients underwent drug sensitivity testing and 20 also completed genomic testing. The median turnaround times were within 10 and 27 days, respectively. Most patients received treatment recommendations (n = 19) and 14 of these patients subsequently received therapeutic interventions.

Additional findings indicated that 5 of the 20 patients who completed the functional precision medicine approach had an actionable treatment recommendation based on genomic variants, with 1 of these 5 receiving a recommendation for cancer-matched therapy. The median reporting time of drug sensitivity testing results following sample receipt was 9 days for hematological malignancies (range, 5-17) and 10 days for solid tumors (range, 4-23); comparatively, the median turnaround time for UCSF500 profiling is 26.5 days (range, 14-63).

“These results are a truly significant advance in personalizing medicine for patients, as it broadens the application of functional precision medicine by being the first prospective study to include both liquid and solid tumors, regardless of cancer type,” Azzam said in another press release. “After a decade of research, this study validates using functional precision medicine data to inform the next line of therapy for children who have exhausted SOC options. We can now provide new hope for those with difficult-to-treat malignancies.”3

“By combining genomics with functional evidence on which drugs work best for each patient’s cancer, we can take truly personalized oncology to a whole new level. “This game-changing platform provides clinicians the critical insights they need to get these children onto more effective therapies sooner,” Noah E. Berlow, PhD, the cofounder and chief technology officer of First Ascent Biomedical, added in the press release.


  1. Groundbreaking treatment approach shows promise in hard-to-treat cancers. News release. Florida International University. April 11, 2024. Accessed April 16, 2024.
  2. Acanda De La Rocha AM, Berlow NE, Fader M, et al. Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers. Nat Med. Published online April 11, 2024. doi:10.1038/s41591-024-02848-4
  3. New study shows functional precision medicine platform identifies effective treatments for 83 percent of children with difficult-to-treat cancers. News release. First Ascent Biomedical. April 11, 2024. Accessed April 16, 2024.
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