April 20, 2020
Researchers from The University of Kansas Cancer Center, the Stowers Institute for Medical Research and Children’s Mercy Kansas City have identified a novel approach to overcome drug resistance in leukemia, using a tried-and-true chemotherapy drug. The study was published in Nature Cell Biology.
The researchers found that low doses of doxorubicin, a standard chemotherapy treatment for several types of cancer including leukemia, inhibit two molecular pathways, Wnt/beta-catenin and PI3K/Akt, which work closely together to promote tumor growth and resistance to therapy. The team also found that low-dose, but not high-dose doxorubicin, activatded anticancer immunity against therapy-resistant leukemia stem cells, an unexpected and novel discovery.
“In low doses, doxorubicin actually stimulated the immune system, in contrast with the typical clinical doses, which were immunosuppressive, killing healthy immune cells indiscriminately,” said John M. Perry, PhD, in a press release issued by Stowers. Dr. Perry is a KU Cancer Center member and researcher with the Children’s Mercy Research Institute at Children’s Mercy.
The research holds promise as a more effective strategy to overcome cancer therapy resistance and stimulate immunity that can be used in combination with other cancer therapies including chemotherapy, radiation and immunotherapy for patients with leukemia and other types of cancer. Low-dose doxorubicin also avoids the harsh side effects of high-dose doxorubicin, including damage to the heart muscle, potentially offering patients a better quality of life.
The research team leveraged the cancer center’s clinical trial expertise to test low-dose anthracycline treatment on adults with treatment-resistant acute myeloid leukemia (AML). The clinical trial was led by Tara Lin, MD, medical director of the cancer center’s Clinical Trials Office. They also utilized the cancer center’s drug development arm, the Institute for Advancing Medical Innovation, to conduct high throughput testing.
The findings are the result of a decade-long collaboration among researchers at the cancer center, Stowers Institute, Children’s Mercy and other institutions. Stowers and Children’s Mercy are members of the cancer center’s National Cancer Institute Consortium partnership.