Drugs for diabetes, inflammation, alcoholism — and even for treating arthritis in dogs — can also kill cancer cells in the lab, according to a study by Massachusetts researchers who tested thousands of approved medicines and experimental compounds in a search for unrecognized cancer-fighting properties.
The study, by scientists at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute, analyzed more than 4,500 drugs and compounds collected in the Broad’s recently established Drug Repurposing Hub. The researchers found that nearly 50 non-oncology drugs killed different human cancer cell lines.
“We thought we’d be lucky if we found even a single compound with anti-cancer properties, but we were surprised to find so many,” said Dr. Todd Golub, a cancer specialist who works as the Broad’s chief scientific officer and helped start the collection.
There’s a big difference between killing cancer cell lines grown in the laboratory and cancer in the human body. But the researchers said the findings, published in the journal Nature Cancer, also revealed novel drug mechanisms and targets. The results could suggest ways to speed the development of new cancer drugs or repurpose existing drugs to treat cancer.
Ordinarily, drug developers identify a target — often a protein in the body — and then hunt for a compound that can alter it to produce a therapeutic effect. The researchers in the Nature study turned that process on its head.
“I think this approach where we flip the order of traditional drug discovery is quite promising,” said Dr. Steven Corsello, a Dana-Farber oncologist and lead author of the Nature paper.
Among the substances that researchers found had cancer-fighting properties was disulfiram, which treats alcohol dependence; tepoxalin, which was developed for people but now treats osteoarthritis in dogs; and vanadium-containing compounds developed to treat diabetes.
The hub was established about three years ago and now features more than 6,000 drugs and compounds that are either approved by the Food and Drug Administration or have been proven safe in clinical trials. (At the time of the study, the collection contained 4,518 drugs). The study marks the first time researchers screened the entire collection of mostly non-cancer drugs for their anti-cancer capabilities.
It’s hardly uncommon for researchers to find a new use for an old medicine. Thalidomide, a morning-sickness drug withdrawn in the early 1960s after it caused birth defects, is now used to treat multiple myeloma, a blood cancer. Sildenafil, developed by Pfizer as a possible blood pressure drug, became the blockbuster impotence medicine Viagra in 1998. Leukine, approved in 1991 to bolster immune systems weakened by chemotherapy, won clearance in 2018 to treat radiation sickness in case of a nuclear explosion.
The researchers tested all 4,518 compounds in the hub on 578 human cancer cell lines. Using a molecular barcoding method known as PRISM, which was developed in the lab, the researchers tagged each cell line with a DNA barcode, allowing them to pool several cell lines together in a dish and more quickly conduct a larger experiment. The team then exposed each pool of barcoded cells to a single compound from the collection, and measured the survival rate of the cancer cells.
The Broad’s officials plan to test the roughly 1,500 compounds that were collected since the study to see if any of those also kill cancer cells.
Among the people hoping that the effort leads to the marketing of new cancer drugs is Prabal Chakrabarti, a senior vice president of the Federal Reserve Bank of Boston. His daughter, Sajni, was diagnosed with an aggressive and rare form of brain cancer, diffuse intrinsic pontine glioma, or DIPG, at the age of 7. There are no approved drugs for the disease. Sajni died in 2017, when she was 9.
Prabal Chakrabarti has helped establish the Sajni Chakrabarti Fund for DIPG at the Broad, which has raised more than $200,000 of the $250,000 needed to start testing the collection on that form of cancer. Researchers have to grow DIPG cell lines a special way and plan to begin testing compounds on that form of cancer soon.
“It’s especially important to me to get this [collection] tested for DIPG,” Chakrabarti said. “The fact that this was in a Nature article, the top journal, shows that this isn’t hype.”
Jonathan Saltzman can be reached at firstname.lastname@example.org.