In a new study, researchers found dozens of non-oncology drugs, including drugs for diabetes, inflammation, alcoholism—and even for treating arthritis in dogs—can also kill cancer cells in the lab.
They analyzed thousands of already developed drug compounds and found nearly 50 that have previously unrecognized anticancer activity.
The surprising findings, which also revealed novel drug mechanisms and targets, suggest a possible way to accelerate the development of new cancer drugs or repurpose existing drugs to treat cancer.
The research was done by scientists at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute.
The new work is the largest study yet to employ the Broad’s Drug Repurposing Hub, a collection that currently comprises more than 6,000 existing drugs and compounds that are either FDA-approved or have been proven safe in clinical trials (at the time of the study, the Hub contained 4,518 drugs).
The study also marks the first time researchers screened the entire collection of mostly non-cancer drugs for their anti-cancer capabilities.
Historically, scientists have stumbled upon new uses for a few existing medicines, such as the discovery of aspirin’s heart benefits.
In the study, the team tested all the compounds in the Drug Repurposing Hub on 578 human cancer cell lines from the Broad’s Cancer Cell Line Encyclopedia (CCLE).
Using a molecular barcoding method known as PRISM, the researchers tagged each cell line with a DNA barcode, allowing them to pool several cell lines together in each dish and more quickly conduct a larger experiment.
The team then exposed each pool of barcoded cells to a single compound from the repurposing library and measured the survival rate of the cancer cells.
They found nearly 50 non-cancer drugs—including those initially developed to lower cholesterol or reduce inflammation—that killed some cancer cells while leaving others alone.
Most of the non-oncology drugs that killed cancer cells in the study did so by interacting with a previously unrecognized molecular target.
For example, the anti-inflammatory drug tepoxalin, originally developed for use in people but approved for treating osteoarthritis in dogs, killed cancer cells by hitting an unknown target in cells that overexpress the protein MDR1, which commonly drives resistance to chemotherapy drugs.
The researchers were also able to predict whether certain drugs could kill each cell line by looking at the cell line’s genomic features, such as mutations and methylation levels.
This suggests that these features could one day be used as biomarkers to identify patients who will most likely benefit from certain drugs.
The researchers hope to study the repurposing drug compounds in more cancer cell lines and to include more compounds that have been tested in humans.
One author of the study is Todd Golub, chief scientific officer and director of the Cancer Program at the Broad.
The study is published in Nature Cancer.
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