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Guided chemotherapy may kill hard-to-reach cancer cells, researchers say

Attaching chemotherapy to an engineered protein in lab experiments with mice increased efficacy of the drugs.

By Stephen Feller
Guided chemotherapy may kill hard-to-reach cancer cells, researchers say
Researchers hope cancer drugs attached to proteins engineered to seek out and bind to tumor cells could help kill cancer while leaving surrounding healthy cells untouched. Photo by UGREEN 3S/Shutterstock

STANFORD, Calif., June 24 (UPI) -- Using an engineered protein, researchers think they can direct chemotherapy to hard-to-reach and treatment-resistant tumors that could help reduce symptoms of the treatment while increasing its efficacy.

Researchers at Stanford University devised two methods of attaching chemotherapy drugs to an engineered protein, finding both were effective at delivering drugs to tumor cells in mice, killing cancer while not harming surrounding healthy cells.

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The goal was to reach tumors farther away from blood supplies, or walled off from them like the brain, because this limits the amount of chemotherapy that reaches cancer cells.

By adding the drug to a protein that seeks to bind to the surface of cancer cells, the drug is led directly to cancer, rather than harming other cells or simply passing through the body with no effect.

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The longer-term hope is the technique will lead to better treatment of brain cancer, which can be difficult to treat because the blood-brain barrier, as well as other forms of the disease.

"These studies showed that we could use these molecules to deliver drugs to tumors," Dr. Jennifer Cochran, an associate professor of bioengineering at Stanford University, said in a press release. "What we still need to understand is which cancers it works best on and what is the best chemotherapeutic drug to use."

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Cochran and the researchers engineered a variant of a protein called knottin, creating a version that binds to molecules on the surface of cancer cells called integrins. From this, they developed two methods of attaching chemotherapy drugs to the re-engineered knottin, testing each for efficacy.

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For the first method, detailed in a study published in the journal Molecular Cancer Therapeutics, the researchers used a portion of an antibody to attach chemotherapy to the knottin. The method is based on antibody therapies already used with patients in the hope it could speed approval if successful.

In the lab, as well as in mice with human tumors, the researchers report knottin delivered its chemotherapy payload to the tumor, killing cancer cells.

The second method, outlined in a study published in the journal Angewandte Chemie, used a chemical link to attach the drug directly to knottin, successfully killing breast, ovarian and pancreatic cancer cells in the lab, including forms of cancer resistant to the drug by itself.

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Future research is required to learn which of the two methods is most effective, the researchers say, adding the early success of both lends promise to delivering drugs directly to tumors in this way.

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