Scientists find unexpected anti-cancer activity in range of non-oncology drugs — study
As the second leading cause of mortality globally, the lucrative field of cancer treatment has elicited a frenzy of drug development and billions in venture funding. But a new study suggests that cancer-killing compounds may be lurking in the existing arsenal of non-oncology medicines.
By analyzing thousands of FDA-approved drugs and compounds that have been proven safe in clinical trials, scientists at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute found nearly 50 compounds — including drugs for diabetes, inflammation, alcoholism and even a treatment for arthritis in dogs — with previously undetected anti-cancer activity.
“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 Todd Golub, chief scientific officer and director of the Cancer Program at the Broad, Charles A. Dana Investigator in Human Cancer Genetics at Dana-Farber, and professor of pediatrics at Harvard Medical School, in a statement.
The study, published in the journal Nature Cancer, employed the Broad’s Drug Repurposing Hub, analyzing 4,518 drugs against 578 human cancer cell lines from the Broad’s Cancer Cell Line Encyclopedia. After tagging each cell line with a DNA barcode, the researchers exposed each pool of barcoded cells to a single compound from the repurposing library and measured the survival rate of cancer cells.
Some of the cancer-slaying compounds kill in unforeseen ways, study lead author Steven Corsello said. Corsello is an oncologist at Dana-Farber and founder of the Drug Repurposing Hub.
Most existing cancer drugs work by stifling proteins — but some of the cancer-killing compounds Corsello et al came across appeared to work by activating a protein or stabilizing a protein-protein interaction. For example, the team found that nearly a dozen non-oncology drugs killed cancer cells that express a protein called PDE3A by stabilizing the interaction between PDE3A and another protein called SLFN12.
The results of the analysis — which scoured nearly half of all drugs ever tested in humans — suggests that some non-oncology drugs could be taken straight into clinical testing in cancer patients, although scientists will need to ensure the cancer culling activity of these drugs is observed at concentrations that are tolerable in humans. It is also imperative to confirm that the predictive biomarkers identified in cell lines represent distinct populations of human tumors, the researchers cautioned.
“In contrast to the repositioning of existing drugs for new indications, the…results reported here also represent starting points for new drug development. In particular, when the anti-cancer activity of a drug occurs via an off-target mechanism, it is likely that further optimization for this new target will result in more potent and selective drug candidates,” the researchers wrote.
Repurposing drugs on purpose (or by accident) has yielded some success — that the process involves largely de-risked compounds, lower developmental costs, and briefer timelines don’t hurt either.
Aside from aspirin’s cardiovascular benefits, Viagra is another heavily cited example. The drug was originally being tested as a treatment for coronary hypertension — but a pesky side effect felt by patients in trials culminated in its eventual approval as an erectile dysfunction drug.
Then there’s the sedative thalidomide — which gained notoriety after its link to severe skeletal birth defects triggered its withdrawal in 1957. However, years later it was deemed effective as a cancer treatment, even breeding the development and approval of even more successful derivatives, such as Celgene’s blockbuster Revlimid.
Meanwhile, Merck’s Vioxx — which was unceremoniously taken off shelves after its link to doubling patients’ risk of heart attack and stroke emerged — could resurface as a generic treatment for a side effect experienced by hemophilia patients.
But akin to traditional drug development, drug repurposing has also seen its share of setbacks. Two examples of late-stage failures include a bid to use the antihistamine, latrepirdine, as a treatment for Huntington’s disease, as well as the pursuit of repurposing the antibiotic, ceftriaxone, as a medicine for ALS.