Jefferson Investigates: September 2026

Androgen deprivation therapy (ADT), often used to treat prostate cancer, is linked with greater risk of metabolic syndrome, which includes metabolic conditions like obesity, insulin resistance, hypertension, and dyslipidemia. However, it’s not clear how combining ADT with androgen receptor pathway inhibitors (ARPIs), a newer treatment also used for prostate cancer, changes this risk.

Understanding how ARPIs influence outcomes is especially important now that the therapy is increasingly used in patients with earlier stages of prostate cancer. “That means there are going to be a lot more patients who are exposed to this therapy for much, much longer periods,” says Grace Lu-Yao, PhD, MPH, a professor in Thomas Jefferson University’s Department of Medical Oncology.

A recent study, led by Amy L. Shaver, PhD, PharmD, MPH, a researcher in Thomas Jefferson University’s Department of Pharmacology, Physiology, and Cancer Biology, measured the timing and occurrence of metabolic syndrome in patients receiving ADT-ARPI who had no signs of the condition prior to treatment. Patients were followed for 12 months after starting concurrent ADT and ARPI treatment and were classified as having metabolic syndrome if they developed at least three of its component conditions or received a physician diagnosis of metabolic syndrome.

Results showed that nearly 40% of participants developed metabolic syndrome, with a median time of 2.6 months to onset. This indicates that metabolic syndrome is both very common in patients taking ADT-ARPI and develops rapidly after initiating treatment.

These findings suggest that patients receiving ADT-ARPI should be actively monitored for metabolic dysfunction. “When a person is being treated for cancer, the treatment for their cancer is critical, but we need to remember that there are other conditions that that person is dealing with,” says Dr. Shaver. “Holistic care and having a unified healthcare team involving the patient is important.” For example, a dietitian or endocrinologist could be included to monitor for changes to cardiometabolic health.

Dr. Shaver plans to conduct a follow-up study that includes a comparison group of patients receiving ADT without an ARPI. “I'd like to better understand the specific contribution of ARPIs to metabolic dysfunction and identify interventions that could best serve these patients,” she says. 

By Zoe Cunniffe

People getting recommended screening tests for one cancer can be reminded about other relevant screenings. It’s a simple way to increase compliance for potentially life-saving tests.

In a new study, Thomas Jefferson University researchers investigated the potential for this kind of intervention for patients enrolled in a lung cancer screening program, directed by Julie Barta, MD,  an associate professor at Sidney Kimmel Medical College.

The study participants were women age 50-75 who are smokers or have a significant smoking history, says Meghan Maceyko, MD, a fourth-year general surgery resident. The recommendation is that they get an annual chest CT (computed tomography) to check for diseases of the lung, including cancer. 

As smokers, these older women are also at heightened risk for breast cancer. “Smoking is a risk factor in all cancers,” Dr. Maceyko says.

The study looked retrospectively at the patients’ electronic health records to see whether the women had gotten a mammogram in the two years before their lung cancer screen. The researchers delved into patient characteristics and found that women with a greater smoking history and those with previous cancer diagnoses were more likely to be overdue for breast cancer screening.

Thus, the highest risk patients seemed to have the lowest adherence to recommended screenings, which points to a “critical gap in preventive care,” the researchers observe.

That gap in care could be addressed by adding a question about breast cancer screening to patients’ intake interviews — a simple intervention that targets those at high risk. “It should be relatively easy to integrate an additional prompt for women,” Dr. Maceyko says. For medical centers that have lung cancer screening programs, like Jefferson Health, the infrastructure is already in place. The next step is to choose an easy and effective prompt, such as a pop-up reminder on a questionnaire or an added question by the intake nurse.

In addition, more research in this area may open further avenues to improve screening adherence, such as prompting questions about other cancer screenings or creating paths for electronic health records to flag overdue tests.

By Jill Adams

Uveal melanoma is a rare and aggressive cancer that starts inside the eye and often spreads to the liver. Few treatment options exist, and unlike some forms of skin melanoma which can respond well to modern therapies, metastatic uveal melanoma (MUM) remains difficult to treat.

Now, a team of Thomas Jefferson University researchers have tested a potential drug combination for MUM in a clinical trial that uncovers clues about why some of these tumors are resistant to treatment.

The study, published in the research journal Cancers, tested two drugs, defactinib and avutometinib, in 12 people with MUM. A novel technology called “synthetic lethality analysis” indicated that this combination should work to block two different pathways and suppress the growth of MUM cancer cells.

Unfortunately, the treatment did not produce the tumor shrinkage the researchers expected. After two treatment cycles, six patients had stable disease, meaning their tumors did not grow, while six patients’ disease worsened.

“We were hoping that this was going to be a miracle combination,” says oncologist and senior author of the study Takami Sato, MD, PhD.

Although it was not what they had hoped for, the researchers saw an opportunity to learn from the unexpected results. They compared tumor samples taken before and after treatment and looked for differences between tumors that remained stable and those that continued to grow.

They saw that levels of an enzyme called ALDH1A3 increased after treatment in several patients whose disease progressed, while patients whose disease remained stable tended to have lower levels. Previous research has linked high levels of ALDH1A3 with treatment resistance.

The team also found that tumors that progressed maintained biochemical signals that help cancer cells survive. These findings could help researchers identify ways to overcome resistance.

“Patients are still desperate, and we will keep looking,” says oncologist and lead researcher of the study Rino Seedor, MD. Indeed, the team is now considering a new combination treatment based on the results of this study.

Together, the study highlights how moving discoveries from the laboratory into the clinic and then bringing what is learned back to the laboratory is “crucial to moving the science forward and developing better therapies,” Dr. Seedor says.

By Roni Dengler