Turning Data into Hope
UVA Comprehensive Cancer Center Director Thomas P. Loughran Jr., MD, and professors in the Division of Hematology and Oncology Charles Chalfant, PhD, and David Feith, PhD, have received a new five-year, $13 million grant from the National Cancer Institute (NCI). With this funding, the team will lead a multi-institutional, interdisciplinary study aimed at developing new therapies for acute myeloid leukemia (AML).
This prestigious NCI award is especially noteworthy, given the increasingly competitive landscape for limited federal research funding. According to the NCI, new funding cuts mean that only about 4% of new NCI applications are likely to receive a grant, and funding for some existing projects may be reduced. Support for new clinical trials will likewise decrease.
“The science has to be exceptionally good to get funding, meaning that you've already proven a lot of the work and you already have a lot of data beforehand to show it will turn out correctly,” said Dr. Loughran. “So, it’s very high-quality science.”
Dr. Loughran and his collaborators will use this new NCI award to gain a deeper understanding of sphingolipids, which are molecules found inside AML cancer cells. These molecules, the scientists believe, are essential for the cancer to grow and spread—and could be its Achilles’ heel. By leveraging nanotechnology, they ultimately aim to deliver a modified form of a specific type of sphingolipid, namely ceramide, to target and kill cancer cells.
“There is a strong clinical need to improve treatment outcomes for AML,” Chalfant said. “Through this award, our team will now be able to build the foundational research to rapidly bring new therapeutic avenues for this disease to the bedside.”
According to Dr. Loughran, receiving this level of NCI funding required demonstrating not only promising preliminary data from earlier experiments, but also the team’s track record of research experience and published results, as well as what Dr. Loughran calls “a provable synergy”—an ability to collaborate across disciplines.
Cancer scientists applying for NCI grants are scored on these merits.
“It’s hard to quantify this kind of grant exactly. It’s a large multi-institutional program project grant. We received a score of 20, which is considered outstanding in their framework. Ten is exceptional. So, we scored very high,” said Dr. Loughran. “It’s extremely hard.”
Beating out stiff competition for the new NCI funding is just the latest example of the Cancer Center’s successful pursuit of solutions to AML, the deadliest blood cancer, which is rare but extremely aggressive. AML is primarily diagnosed in patients with a median age of 68, occurring when myeloid cells mutate and multiply in the bone marrow and blood, crowding out the healthy blood cells that carry oxygen, form clots, and fight infections.
Treatment options for these patients include chemotherapy, stem cell transplants, drugs targeting proteins that support the cancer’s growth, and a growing number of combination therapies. While chemotherapy is the traditional first-line method, its effectiveness varies between cases, it’s less well-tolerated by older patients, and therapy resistance is prevalent, which demonstrates the need for new and more tailored treatments.
“We’re really working hard and looking forward to helping these patients who don’t really have another course of treatment,” Dr. Loughran said.
In previous studies, Dr. Loughran and collaborators Kevin Janes, PhD, and Bishal Paudel, PhD, found that they could measure sphingolipids in patients’ cells to determine whether the patients would be resistant to chemotherapy and should consider alternative treatments or a clinical trial.
“Right now, it can be kind of fuzzy on whether a certain patient is at risk of poor outcomes. This new way we found of classifying AML has implications for what kind of treatment you might deliver to that patient,” said Dr. Loughran.
Thanks to the support of a private donor, the Cancer Center has launched a new multisite clinical trial testing this approach under the leadership of Michael Keng, MD, an associate professor in the Division of Hematology and Oncology.
“The science is astonishingly effective as far as we can tell, so we are optimistic,” Dr. Loughran said.
Those affected by AML may find hope in these extensive inroads UVA’s scientists and physicians are making. None of it would be possible without federal and state research funding, as well as ongoing private support from visionary donors inspired by the potential of the Cancer Center’s scientists to make a difference. According to Dr. Loughran, private funding is often the primary source of support for the early experiments and initial data collection required to secure larger institutional grants.
“We’ve made great progress understanding how AML works and how patients respond to treatment differently,” Dr. Loughran said. “This new project will build on that, drawing on disciplines ranging from hematology to the engineering of nanotechnology to deliver new therapies directly to cancer cells. We’re thrilled to continue this collaborative work to reduce the impact of this devastating disease.”