One of the largest problems with cancer treatment is the development of resistance to anticancer therapies. A research team found that repurposing a commonly used chemotherapy drug using a nanoparticle was more effective than both a solution of the pure drug and other available treatments.

One of the largest problems with cancer treatment is the development of resistance to anticancer therapies. Few FDA-approved products directly target leukemia stem cells, which cause treatment-resistant relapses. The only known method to combat their presence is stem cell transplantation.

Leukemia presents unique treatment challenges due to the nature of this form of cancer. The disease affects bone marrow, which produces blood cells. Leukemia is a cancer of the early blood-forming cells, or stem cells. Most often, leukemia is a cancer of the white blood cells. The first step of treatment is to use chemotherapy to kill the cancerous white blood cells, but if the leukemia stem cells in the bone marrow persist, the cancer may relapse in a therapy-resistant form.

Fifteen to 20% of child and up to two thirds of adult leukemia patients experience relapse. Adults who relapse face a less-than 30% five-year survival rate. For children the five-year survival rate after relapse is around two thirds. When relapse occurs, chemotherapy does not improve the prognosis for these patients. There is a critical need for scientists to develop a therapy that can more effectively target chemotherapy-resistant cells.

There are two cellular pathways, Wnt- ?-catenin and PI3K-Akt, which play a key role in stem cell regulation and tumor regenesis. Cooperative activation of the Wnt- ?-catenin and PI3K-Akt pathways drives self-renewal of cells that results in leukemic transformation, giving rise to cancer relapse. Previous studies have worked on targeting elements of these pathways individually, which has had limited success and often results in the growth of chemo-resistant clones.

The researchers screened hundreds of drugs to find one that may inhibit this interaction. They identified a commonly used chemotherapy drug, doxorubicin as the most viable target. While this drug is highly toxic and usually used with caution in clinical settings, the team found when used in multiple, low doses, it disrupts the Wnt- ?-catenin and PI3K-Akt pathways’ interaction, while potentially reducing toxicity.

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