Researchers were seeking a promising new strategy to challenge drug resistance in leukemia. They found that targeted low doses of the widely-used chemotherapy drug doxorubicin is effective in overcoming resistance by leukemic cells.
"In low doses, doxorubicin actually stimulated the immune system, in contrast with the typical clinical doses, which were immunosuppressive, killing healthy immune cells indiscriminately," says John M. Perry, PhD, a researcher with the Children's Mercy Research Institute at Children's Mercy. He completed his postdoctoral work at Stowers and is first author of the report.
Doxorubicin is an anthracycline antibiotic that inhibits the interaction of two molecular pathways— Wnt/beta-catenin and PI3K/Akt--that promote tumor growth.
"Our idea was to find a drug with the goal of blocking the interaction between Wnt/beta-catenin and PI3K/Akt and reduce the toxicity," says Stowers Institute Investigator Linheng Li, PhD.
Findings were published in the journal Nature Cell Biology.
"We found that mice receiving patient sample transplants with therapy-resistant leukemia stem cells rapidly developed leukemia, but low-dose doxorubicin treatment improved survival by reducing leukemia stem cells," Perry says. "However, mice receiving patient sample transplants that did not contain therapy-resistant leukemia stem cells did not respond to low-dose doxorubicin treatment. These results showed that chemoresistant leukemia stem cells from patients could be functionally reduced with low-dose doxorubicin treatment, at least in an in vivo animal model assay."
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"The research holds promise as a more effective strategy to overcome cancer therapy resistance and immune escape that can be used in combination with other cancer therapies including chemotherapy, radiation, and immunotherapy for patients with leukemia and other types of cancer," Li says.
Source: Science Daily