Custom-made DNA-crafted drugs improve cancer outcomes, per UC San Diego study

By using a patient’s DNA to craft personalized drug treatments, doctors can increase the efficacy and better the outcomes of fighting cancer, according to a UC San Diego School of Medicine-led study released Thursday.

The study, published in Thursday’s online edition of Journal of Clinical Oncology, found that by tailoring a multi-drug treatment to each patient’s specific tumor mutations, doctors can greatly enhance the success of treatment.

“Every patient and every cancer is unique, and so should how we treat for them,” said Dr. Jason Sicklick, senior author of the study, professor of surgery and pharmacology at UCSD School of Medicine and surgical oncologist at UCSD Health. “Our findings demonstrate that precision oncology at the individual level is achievable. When every patient’s treatment is guided by their tumor’s distinctive DNA, we can treat cancer with better accuracy.”

The clinical trial — the Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) — used advanced genomic sequencing to identify the molecular changes driving an individual’s cancer. Doctors then created personalized treatment plans using FDA-approved drugs, with doses “carefully adjusted for each patient to precisely target those molecular alterations,” the opposite of a one-size-fits-all approach, the researchers said.

Among 210 patients with advanced cancers that were studied and treated, almost 95% had totally distinct tumor profiles. This led to 157 different treatment regimens, including 103 new drug pairings that had never been tested together before, a statement from UCSD read.

According to the findings, those patients whose treatments were closely matched to their tumor mutations saw better results, improving their chances for response and survival.

Additionally, those who received new drug combinations did not experience more severe side effects than patients receiving standard therapies.

“The I-PREDICT study shows what’s possible when we let a patient’s biology guide their treatment,” said Dr. Shumei Kato, associate professor of medicine at UCSD School of Medicine and medical oncologist at UCSD Health. “By using biomarkers to select drugs and adjust doses, we can design combinations that precisely target the drivers of each person’s cancer.”

The researchers found by beginning new drug mixes at lower doses and carefully increasing them over time kept treatments safe, even with therapies that had never been used together before.

“Innovative clinical trial design is a central part of what we do at Moores Cancer Center,” said Dr. Diane Simeone, director of Moores Cancer Center at UCSD Health. “This study reflects the strength of our multi- disciplinary team-based approach, combining scientific leadership, clinical trial expertise and the infrastructure needed to bring discoveries directly to patients.

“It’s a powerful example of how we’re shaping the future of precision oncology and placing the patient at the center of every decision.”

The Moores Cancer Center was a key partner in the clinical trial.

Sicklick, who is also co-leader of the structural and functional genomics program at Moores Cancer Center, said this research marks a turning point for cancer treatment.

“Instead of a one-size-fits-all, we’re moving toward one-size-fits-one,” he said.

Building on I-PREDICT data from 2019 and 2022, the UCSD study could lead to a future randomized trial designed to “confirm the benefits” of the personalized approach to cancer.