Jefferson Investigates: July 2026

Acute myeloid leukemia (AML) is an aggressive blood cancer that remains difficult to treat. While targeted therapies have improved outcomes for some patients, many relapse when a small population of cancer stem cells survives treatment and seeds the disease again. 

Now, researchers at Thomas Jefferson University have identified a three-drug combination that nearly eliminates cancer cells that are resistant to current treatments. The findings raise hopes for a more durable therapy.

The research, published in Science Advances, focused on a drug called inobrodib, which has shown promise in early clinical trials. However, previous studies suggested it would likely need to be combined with other therapies to achieve a lasting effect.

“AML is a really challenging disease, and even the newest targeted therapies are often most effective when used in combination,” says cancer biologist and senior author of the study Sara Meyer, PhD. “The question became: what should we combine inobrodib with?”

The research confirmed that inobrodib slowed leukemia growth and extended survival in mice with AML. But the drug on its own was not enough to eliminate leukemia stem cells—the cells that cause leukemia, therapy resistance and cancer relapse.

“Those stem cells are a major reason why AML comes back,” says graduate student and first author Melanie Goetz. “Our goal is to develop therapies that can target them.”

When the team paired inobrodib with two FDA-approved drugs, venetoclax and gilteritnib, the results were striking. The three-drug regimen produced more cancer cell death than any single drug or two-drug combination tested. Mice receiving the triple drug combination had roughly 10 times fewer leukemia stem cells remaining in their bone marrow than mice receiving the next most effective therapy. The combination also triggered extensive cancer cell death in samples from AML patients.

“This is exactly the kind of preclinical work that can translate directly into new therapies for patients,” says Dr. Meyer.

Dr. Meyer and team are now working with clinicians, collaborators, and the drug manufacturer of inobrodib to explore a future clinical trial for patients with relapsed or treatment-resistant AML.

“For many of these patients, survival is often measured in months,” Dr. Meyer says. “We hope this approach could offer them a new opportunity with better outcomes.”

By Roni Dengler

New research from Thomas Jefferson University shows that greater cumulative exposure to adverse social determinants of health is associated with beliefs that cancer is unavoidable or is a death sentence. This can influence whether people choose to be screened for common cancers or seek treatment after diagnosis.

The study looked at survey data from Sidney Kimmel Comprehensive Cancer Center – Jefferson Health about cancer beliefs and social risk factors. Researchers considered the effects of race, sexual identity, food insecurity, housing insecurity, socioeconomic status, health insurance status, education level, social isolation and discrimination. The findings were published in the Journal of Psychosocial Oncology.

Among the 1,400 respondents from seven counties in Pennsylvania and New Jersey, 29% lived below the poverty level, 17% experienced housing insecurity and 15% had no health insurance.

The study is the first to show that cumulative adverse social risk factors correlate with increased cancer fatalism.

“Belief of fatalism is thinking you’re unable to do anything about it; if you are diagnosed, you’re going to succumb to your disease anyway, so why bother getting treatment,” says Nicole Simone, MD, the study’s senior author. “For example, some people don’t follow up on abnormal screenings.”

The study is also among the first to examine the total burden of social determinants on cancer beliefs. Previous research considered one or two factors, but it wasn’t representative of the real-world impacts of every adverse social factor.

“We made a continuum, looking at the total number of adverse events,” Dr. Simone says. “If you were above the median of two adverse effects, you were more likely to have that fatalistic attitude.”

The study’s findings suggest the importance of standardizing protocols to screen patients’ social risk factors.

“At our cancer center, a patient care coordinator or nurse asks those screening questions so we have baseline information,” Dr. Simone says. “This helps us identify at-risk patients.”

Jefferson radiation oncology resident Ayesha Ali, MD; post-baccalaureate student Sarah Burke; and medical students in Jefferson’s summer oncology program – Jaitri Joshi, Alexandria Smith, Brittany Smith and Kamryn Hines – contributed to the research.

By Lisa Fields

Neck and low back pain affect millions worldwide and is a top factor of living with disability. Degeneration of the discs that cushion the spine is a leading cause. Current treatments can relieve symptoms but do little to slow the underlying disease. Now, researchers from Thomas Jefferson University have shown that targeting harmful, aging cells early may preserve disc health and delay degeneration.

The study, published in Bone Research, focused on cellular senescence, a state in which cells become dormant but still release inflammatory molecules that can damage surrounding tissue. While senescence is a hallmark of aging, the researchers wanted to determine whether it also contributes to disc degeneration that begins earlier in life.

The team found that the cells in spinal discs of young mice with early-onset degeneration looked like the senescent cells of much older mice. The findings indicated that there may be an opportunity to intervene before the disease sets in.

“This study demonstrates for the first time in animals that cell senescence may play a pathological role in early onset disc degeneration,” says cell biologist and senior author of the study, Makarand Risbud, PhD.

The researchers then tested a combination of the drugs dasatinib and quercetin (DQ) to target senescent cells. They found mice treated with DQ had healthier discs, lower levels of inflammation and tissue scarring, and more of the specialized cells needed to maintain healthy spinal discs.

To better understand why the combination drug worked, the researchers analyzed gene activity in the discs. They found that DQ reduced activity in genes linked to inflammation, cell death and cellular aging. The results also identified a signaling pathway known as JUN as a potential driver of degeneration. Blocking JUN activity in human disc cells reproduced many of the protective effects seen with DQ treatment.

Together, the findings suggest that removing senescent cells early may help slow disc degeneration before irreversible damage occurs.

“We are excited by these findings,” says Dr. Risbud. Because dasatinib and quercetin have already been studied in people for other age-related conditions, the approach could eventually be explored as a treatment for disc-related low back pain.

By Roni Dengler