There’s an urgency in Anupriya Agarwal’s voice when she talks about her acute myeloid leukemia research: “We need to do something beyond what we’ve already done,” she said. “The treatment hasn’t changed in decades, and that can’t be our only answer.”
The standard therapy for the last 30 years has been chemotherapy, and researchers like Anupriya Agarwal, Ph.D., assistant professor of medicine (hematology and medical oncology) in the OHSU School of Medicine and researcher with the OHSU Knight Cancer Institute, are working to find new treatment options for those living with the disease.
Due to its heterogeneous nature, AML is particularly difficult to treat and has a low survival rate: less than 25 percent of newly diagnosed patients survive beyond five years.
Rather than focus on the cancer’s genetic drivers — a practice that has become popular since the advent of imatinib, or Gleevec, for chronic myeloid leukemia treatment — Agarwal and colleagues made the decision to concentrate their research on the immediate surroundings, or microenvironment, of AML cells.
“After imatinib, the momentum in the oncology research space shifted to targeted therapy,” she said. “Now people are starting to look at the tumor microenvironment. We need to continue targeted treatment and research, of course, but with a complicated disease like AML, we need to understand the contribution of both genetic and surrounding environmental factors to the disease’s growth.”
One important piece of the microenvironment is the identification of signaling pathways that drive the growth of AML. Agarwal and team identified a specific pathway — Interleukin-1, or IL-1 — that is actively involved in the growth of AML cells. The research team sought to better understand the molecular basis of the pathway in order to target it therapeutically.
In this study, published today in Cell Reports, they found levels of secreted IL-1 and its receptors are significantly increased in AML. The team then blocked the IL-1 pathway, which led to a significant suppression in the in vivo disease progression in mice and in vitro growth in primary AML samples. The IL-1 had a paradoxical growth effect on leukemia versus healthy cells, providing inspiration for further study and, potentially, clinical development of IL-1 pathway-targeted therapy for AML treatment.
Agarwal’s work is a prime example of AML research underway as part of a multi-institution collaboration effort called the Beat AML initiative. The OHSU Knight Cancer Institute is one of several cancer institutes across the country partnering with the Leukemia & Lymphoma Society to seek new treatments for the disease; the collaboration takes a next-generation personalized medicine approach to accelerate research findings and improve outcomes for patients with AML.
Agarwal and team evaluated 60 AML patient samples from the Beat AML initiative for this particular study. Agarwal initiated her own lab in 2014 and says having access to Beat AML sample resources is incredibly valuable.
Particulars: This study received funding from the Knight Cancer Pilot Project, NIH grant 5R00-CA151670-05, and the V Foundation. Study co-author Brian Druker, M.D., director of the OHSU Knight Cancer Institute, is a Howard Hughes Medical Institute Investigator.