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Researchers find cancer-fighting potential in non-cancer drugs

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U.S. researchers who tested the cancer-fighting properties of more than 4,500 non-cancer drugs found nearly 50 drugs for other conditions showed at least some cancer-killing ability.

“We found that a surprising number of non-oncology drugs are able to kill cancer cell lines in the lab,” said Dr Steven Corsello of Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard University, who led the research.

Dr. Bruce Bloom of Healx, a company based in Cambridge, UK that uses artificial intelligence to discover drugs for rare diseases, told Reuters Health by email the new drug targets and mechanisms of action identified by the researchers could be valuable both for new treatment approaches and for repurposing older drugs.

Published this week in Nature Cancer, the work is the largest yet to use the Broad Institute's Drug Repurposing Hub, a collection of samples of more than 6,000 drugs and compounds that are either approved by the U.S. Food and Drug Administration or have gone through early-stage clinical trials proving they are safe in people.

The researchers tested the drugs on more than 550 different cancer cell lines.

Earlier efforts at this kind of discovery have been painstaking because researchers had to grow cell lines one at a time and test each drug individually. This time, they used DNA barcodes - introducing unique snippets of DNA with a virus to label the cell lines. This technique allowed them to pool the cell lines, shortening screening time.

“We tested 4,518 compounds in this experiment in total,” Corsello, founder of the Drug Repurposing Hub, said in a telephone interview. “We found 49 non-oncology drugs that were able to selectively kill cancer cell lines - killing some but not other cancers, which is an ideal property.”

The researchers selected four of these drugs to undergo more testing to better understand how they attacked and killed cancer cells. These included a treatment for diabetes, a drug for inflammation, a treatment for alcohol abuse and one for treating arthritis pain in dogs.

Most of the drugs they tested attacked cancer in novel ways.

The drug tepoxalin, for example, which was originally developed for use in people but later approved for treating osteoarthritis in dogs, worked by attacking a target called MDR1 that’s expressed on the surface of cells and protects them from chemotherapy.

Corsello said cancer patients who develop resistance to chemotherapy often have high levels of this protein.

Antabuse, a drug approved to treat alcohol dependence, showed activity in cancers that lack a portion of chromosome 16, which commonly occurs in some breast cancers.

Other drugs showing anti-cancer properties included a compound originally developed to treat diabetes called vanadium, and levonorgestrel, a hormone used in contraceptives.

Corsello’s team plans to conduct animal studies on some of the drugs to see which have the best chances of success in a clinical trial, and they plan to test even more cancer drugs for anti-cancer properties.

He sees the approach being useful in two ways. In limited cases in which the drug is promising enough, the treatment could be quickly brought into clinical trials in cancer patients. But Corsello believes the more likely use is to identify new and unexpected molecular targets that could lead to cancer treatments.

Bloom, who was not involved with the study, said the paper “highlights the struggle to balance transparency and sharing of discoveries, with heavily patent-dependent commercialization requirements for therapies to make it to market.”

He said while the data support the repurposing of non-oncology drugs to oncology and could lead to even more discoveries, the disclosure of specific drug names and targets might make it harder for companies to protect future repurposed and new treatment discoveries.

© Thomson Reuters 2020.

©2020 GPlusMedia Inc.

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