Redefining Personalized Cancer Treatment

“Alright, it’s going to be a late night,” Diana Azzam tells her research group. The call has just come in from the clinical trial coordinator at nearby Nicklaus Children’s Hospital with an update: A four-year-old girl with metastatic osteosarcoma was soon scheduled to undergo a lung biopsy. Azzam’s lab can expect to receive the sample within hours.

Go time. All hands on deck. Palpable energy sweeps across the room — excitement intermingled with a deep sense of responsibility. Everyone knows what they need to do. And they do it. Workstations are painstakingly prepped, organized. Dinner orders, placed; hunger an unnecessary distraction to the work ahead. Anxiously, Azzam’s team waits.

“Receiving a sample brings so many emotions,” Azzam admits. “We always remember there’s a person behind it, someone we may be able to help, so we’re filled with excitement and hope.”

Golden evening light fills the lab’s floor-to-ceiling windows as the courier arrives with a small white box weighing no more than a few pounds, unassuming if not for the fluorescent reddish orange biohazard warning label adhered to the side. The outside world shrinks, pales in comparison to what’s nestled inside: one test tube containing the freshly collected tissue sample, one vial of blood.

Thanks to a combination of advanced technology, this is all Azzam’s team needs from a patient to pinpoint which drugs will work against their cancer and provide those recommendations to the patient’s physician. From start to finish, the process takes a little under a week. When it comes to controlling diseases that masterfully shapeshift and spread to stay alive, every second counts.

Results, so far, have been nothing short of astonishing. Nature Medicine published findings from the team’s first-of-its-kind clinical trial that examined the impact of functional precision medicine guided treatments for a small group of 25 pediatric patients with hard-to-treat, relapsed blood and solid tumor cancers. Genomic profiling identified actionable mutations in 5% of the children. Drug sensitivity tests turned up recommendations for all of them. Of those who received guided treatments, 83% showed improved outcomes in response and survival over the course of the study.

“The take home message is we can use this approach to direct the next line of cancer therapy for children and adults,” says Azzam, who oversees the Center for Advancing Personalized Cancer Treatments at the FIU Robert Stempel College of Public Health & Social Work. “This is feasible. It works.”

Today, Azzam’s group is among a handful scattered across the globe demonstrating that functional precision medicine can work in the real world. Recently, she’s been hearing from other scientists doing similar work with equally amazing outcomes, except they aren’t widely sharing their discoveries in academic or medical journals.

“Please publish,” Azzam advises. “We can’t do this on our own. We need others to publish and together we will move the field forward.”

What happened after the study landed on Nature Medicine’s April cover can best be described as a whirlwind. News media across the globe picked it up. Invitations to conferences followed. Doctors reached out, encouraged by the data. Even Neil, the FedEx driver who makes frequent deliveries to the lab, knows what’s at stake — on one occasion, going out of his way to ensure a sample could be delivered to the team on time.

The overwhelming response has certainly come as a surprise. More than anything, it “reinforced that we’re genuinely making a difference in children’s lives,” says Arlet M. Acanda de la Rocha, a research assistant professor in Azzam’s lab who handled and processed the initial samples from the first clinical trial. “And saving them.”

Acanda de la Rocha is referring to Patient 13, a case involving a boy with acute myeloid leukemia.

His doctors enrolled him in Azzam’s clinical trial and implemented the recommendations. First, to remove an unnecessary toxic medication from his chemotherapy regime. And also remove steroids that weren’t working as intended in his system, instead making his cancer cells grow exponentially. Within 33 days, Patient 13 reached remission. Two years later, he’s still cancer-free.

No wonder the work stays close to Acanda de la Rocha’s heart. Although her current focus is searching for new therapeutic targets for glioblastoma, the deadliest form of brain cancer, she drops what she’s doing to help with the growing number of patient samples from Azzam’s ongoing clinical trials for both adults and children. It’s another chance at helping another person. And another chance to show the exciting possibilities functional precision medicine holds for the future of oncology, especially to physicians who may still be on the fence about it.

Dr. Jorge Manrique-Succar, a surgeon specializing in orthopedic oncology at Cleveland Clinic Florida, provides perspective on the hesitancy: “As doctors and surgeons, we’re used to doing things by the book” — following standard of care, the well-studied, statistically proven regime that benefits many people — because “you can be blamed for doing the wrong thing even if your intention is always doing the right thing for your patients.”

Manrique-Succar faces the brutal realities of cancer every day. He treats sarcomas, rare types of cancers that develop in bone, cartilage, tendons and more. Sometimes he’ll successfully remove a tumor, a procedure that can require amputation of an arm or leg. It’ll look like the patient is in the clear. Months later, cancer returns elsewhere in the body and there’s fewer treatment options available.

“It’s just unfair. You have a patient who doesn’t have any other medical issues, never smoked or anything, and here they are with metastatic sarcoma.” Some of these patients are currently enrolled in the clinical trial for adults with all types of relapsed cancers.

Immediately after Azzam approached Manrique-Succar about partnering on this study, he wanted to be a part of it.

Each day, on average, he sees around 30 patients in the clinic and may operate on only 6 or so. Research widens the impact he can have on people, especially “this kind of practice-changing research that can truly impact patient care,” he says. 

“I think this approach to individualized treatment is a gamechanger for cancer management. It makes sense, there’s logic to it and we’re using proven medications.”

Manrique-Succar, like Azzam, imagines the potentially greater benefits for newly diagnosed patients — a treatment of first choice not last resort. “Obviously, what I’d like is that we can do this testing at the very beginning, as soon as the tumor is found,” he says.

Azzam never set out to treat cancer in this manner. Initially, she was studying therapy-resistant cancer stem cells. Chemotherapy, radiation, you name it — frustratingly, they survive it. As a postdoctoral researcher, she joined a well- established drug discovery team with the goal of developing new drugs to take out these therapy-resistant cells. Surrounded by state-of-the-art high-throughput screening technology, a question popped into Azzam’s head: Is this available to people with cancer or in a clinical setting?

“The answer was no. It shocked me,” she remembers. “I told myself, ‘Okay, I need to learn everything I can and try to bring these technologies closer to cancer patients.’”

That happened in 2016 when Azzam started her lab at FIU. Funding from the Florida Department of Health - Live Like Bella Pediatric Cancer Research Initiative got the first groundbreaking clinical trial, in collaboration with Nicklaus Children’s Hospital, off the ground. A $2 million appropriation from the State of Florida helped acquire the robotic drug testing equipment.

Ebony Coats, Azzam’s lab manager, nicknamed it “Optimus” after the beloved, brave and wise Transformers hero. Appropriately fitting, considering all it does to help. “It’s basically a member of our team,” she smiles.

Coats wears many hats. Her main job is ensuring everything with the samples runs smoothly. She explains the process as if she could do it in her sleep: Before cells ever meet a single drug inside of the workstation, the tissue sample is bathed in special enzymes. Large chunks of a tumor are not necessary. Amazingly, stringy and delicate tissue from a non-surgical fine needle biopsy will do, which makes testing widely accessible to more patients.

Prepared cell culture models are stored in the incubator at a familiar-to-them 98.6° F. Coats continuously checks to make sure the cells are “happy, healthy and unstressed,” growing like they would in the body, before giving them the greenlight for testing.

Then, they get added to a plate with more than 380 separate wells; drugs to another. Optimus sandwiches them together: cells on top, facing the drugs down below. The transducer shoots out a small burst of sound, causing an imperceivable 2.5 nanoliter drug droplet to leap up into the cell plate. Within three to four hours, a full drug library can be tested.

Azzam’s lab once received about two to three samples a month. They are up to that same number each week. Soon, there will be more. The lab is set to become the first dedicated to functional cancer drug testing in Florida. Most important, testing will be open to people outside of Azzam’s current clinical trials.

It can’t happen soon enough.

Pleas for help from cancer patients and their families fill Azzam’s inbox daily, seeking enrollment in her trials. There’s been hundreds. Every story is different, but each one breaks her heart because all Azzam and her team want is to be there for people who need them. No matter the hour or day. No matter the obstacle or distance.

“We owe this to them. They’re counting on us to keep pushing this forward.”