Targeting Glycolytic Metabolism in Canine B-cell Lymphoma to Remodel the Tumor Microenvironment and Enhance Chemotherapy Response
Principal Investigator: Jessica Hayward
DESCRIPTION (provided by applicant):
B-cell lymphoma (BCL) is a common and aggressive cancer in dogs that closely resembles a type of human
lymphoma called diffuse large B-cell lymphoma (DLBCL). While treatments like chemotherapy can help, many
dogs eventually stop responding, and we still don’t fully understand why. Recent research, including our own,
suggests that cancer cells survive therapy by changing how they use energy. In particular, they rely heavily on
a process called glycolysis, which produces high levels of a waste product called lactate. This buildup of lactate
doesn’t just fuel the cancer; it also weakens the immune system’s ability to fight it.
Our study focuses on a simple, safe dietary supplement called L-arginine. In previous work, we showed that Larginine helps the body produce nitric oxide (NO), which interferes with cancer metabolism and makes tumors
more sensitive to treatments like radiation. We now want to see if this same strategy can help dogs with
lymphoma respond better to chemotherapy.
Using a combination of mice models and immune cell studies, we aim to test whether L-arginine can reduce
lactate levels in tumors, make cancer cells more vulnerable to chemotherapy, and reactivate the dog’s immune
system, especially immune cells that are usually suppressed by the tumor environment. If successful, this
research could pave the way for a new, low-cost combination therapy that improves outcomes in canine BCL,
with promising implications for both veterinary and human medicine.
