Functional precision medicine—in which information is obtained from direct perturbations of tumor-derived living cells that enable immediate translatable, personalized data to guide patient therapy—has its roots dating back more than 50 years.1 However, advances in two- and three-dimensional culture technology may soon establish the approach as a standard tool in clinical oncology.1
Diana J. Azzam, PhD
A small, observational, proof-of-concept study by Diana J. Azzam, PhD, and colleagues investigated the feasibility of functional precision medicine in guiding treatment in pediatric patients with relapsed or refractory cancers. The study findings showed that five of the patients (83%) who received functional precision medicine–guided treatments experienced an improvement in progression-free survival greater than 1.3-fold; and 83% of patients also achieved a significant increase in objective response rate compared with their previous treatment regimen, vs 13% of patients in the physician’s choice treatment cohort.2
The primary objective of the study was to determine the feasibility of returning functional precision medicine–based treatment recommendations for each patient in real time to the interdisciplinary functional precision medicine tumor board within a clinically actionable time frame of up to 4 weeks. The secondary objective was to assess clinical outcomes from the study participants.
In the study, 25 patients (with a median age of 10) who had relapsed or refractory solid or hematologic cancers were enrolled in the trial after exhausting standard-of-care options. A total of 21 patients underwent drug sensitivity testing of their patient-derived tumor cells, and 20 also completed genomic profiling. The patients had had between two and six prior lines of therapy. The study included patients with acute lymphoblastic leukemia, acute myeloid leukemia, astrocytoma, ependymoma, malignant rhabdoid tumor, neuroblastoma, osteosarcoma, rhabdomyosarcoma, kidney cancer, and Wilms tumor. The median turnaround times for drug sensitivity testing and genomics testing were within 10 days and 27 days, respectively. A total of 19 patients received treatment recommendations, and 14 of these patients subsequently received therapeutic interventions.
“We’ve made a lot of advancements in how we grow tumor cells in the laboratory, which is similar to how they grow in the body, and in the technologies we have today in terms of the time it takes to dispense very small volumes of drugs on tumor cells,” said Dr. Azzam, Assistant Professor, Environmental Health Sciences, and Director of the Center for Advancing Personalized Cancer Treatments at Florida International University in Miami. “In addition, we have many more U.S. Food and Drug Administration (FDA)-approved drugs to treat cancer. These advancements in technologies and the way we grow tumor cells in the laboratory are enabling us to generate amazing data, showing that functional precision medicine could be used to impact patient care and clinical decision-making.”
In an interview with The ASCO Post, Dr. Azzam discussed the role of functional precision medicine in clinical care, the barriers to this approach becoming standard of care in oncology, and the next steps to getting functional precision medicine approved by the FDA.
Identifying the Most Effective Treatment for Individual Patients
Please describe functional precision medicine’s role in cancer care.
As we know it today, precision medicine commonly uses DNA analysis or genomics to identify tumor mutations and then tries to find matched treatments for those mutations. In functional precision medicine, we are integrating genomics molecular profiling with drug sensitivity testing. We test hundreds of FDA-approved drugs directly on a patient’s own living cancer cells to identify the right treatments for that person.
Chemosensitivity assays, in which a laboratory test measures the number of tumor cells that are killed by a specific chemotherapy, are not new. They’ve been around for 20 years, but they were very primitive in nature. Advancements in technologies have enabled us to generate promising data showing that functional precision medicine approaches could potentially impact patient care.
I am a board member of the newly created Society for Functional Precision Medicine (https://www.sfpm.io). Members are coming together from laboratories around the world to raise awareness about how functional precision medicine assays have advanced. We will soon start to see a slew of new studies using functional precision medicine drug testing, which will provide more proof that we should start considering the use of these tools for standard clinical decision-making.
Increasing the Number of Drugs for Cancer
How many drugs were tested in your study of pediatric patients with relapsed or refractory cancers using functional precision medicine?
We derived data from tumor panel profiling and functional ex vivo drug sensitivity testing of up to 125 FDA-approved drugs. We customized the drug library tailored to what is available in the pharmacy at the Nicklaus Children’s Hospital in Miami, the main trial site. We had 40 formulary drugs available from this hospital, which is important because we want to make sure the drugs that are effective are actually available to the patient. We included both cancer and noncancer drugs that show evidence against the disease to increase our library of drugs.
Personalizing Cancer Care
Will artificial intelligence (AI) tools help expedite research in functional precision medicine?
Yes, absolutely. The way to advance this research is to integrate functional precision medicine, genomics, and AI to accurately identify novel biomarkers; then the goal is to match them with effective drugs and predict combinations for each individual patient based on the tumor’s genomics and DNA sequencing. The more data we can generate, the better we will be able to train AI algorithms in functional precision medicine approaches and, hopefully, truly personalize cancer care for patients in the future.
Moving Functional Precision Medicine to the Upfront Setting
Is the functional precision medicine technique more likely to be used in the relapsed setting than in the first-line setting for newly diagnosed patients?
Before we can get to the upfront setting with functional precision medicine, we have to perform all of the studies that are needed to show the approach is appropriate in the first-line treatment. However, my goal is to see this method used upfront, especially for cancers we know don’t have effective standard-of-care options.
Overcoming Barriers
What are some of the barriers to conducting this type of research in functional precision medicine?
One big challenge is physician hesitancy in using this method for treatment decision-making. We had only six patients in our study who were guided by functional precision medicine. So, we certainly need to do a better job of raising awareness among physicians about the potential of this approach and the data it can provide to help physicians make informed treatment recommendations. It is important that physicians collaborate with researchers to get these new tools and technologies into clinical care faster, which is also a challenge in genomics precision medicine.
The second big hurdle is getting this testing covered by health insurance companies. To accomplish that goal, we definitely have to show that not only can functional precision medicine improve outcomes for patients, but it can also save money by reducing treatment trial and error.
In addition to more research in functional precision medicine, we need to conduct health economic studies using this method to show how it could reduce medical costs. We will be launching such studies soon, and then, of course, we need to get FDA approval.
Testing Functional Precision Medicine Against Standard Approaches
What is the next step in your research of functional precision medicine?
Currently, I have feasibility studies open in both adult and pediatric cancers, and I’m scaling up with larger numbers of patients. The next important step is to open a large, randomized, multicenter interventional clinical trial in which we could test the clinical utility of functional precision medicine compared with other approaches. And that is going to happen soon.
We are also researching getting more functional precision medicine assays certified, which will lay the groundwork for FDA approval. So, this technology is moving along rapidly and will bring us closer to truly personalizing oncology care for patients.
DISCLOSURE: Dr. Azzam is cofounder of and shareholder in First Ascent Biomedical.
REFERENCES
1. Letai A, Bhola P, Welm AL: Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell 40:26-35, 2022.
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 30:990-1000, 2024.
