In a laboratory, drugs meant for the treatment of alcoholism, inflammation and diabetes can kill cancer cells, claims a new study. What is more exciting is that the study also suggests that drugs used for treating arthritis in dogs can do the same task as well.
Systematically analyzing thousands of drug compounds that have already been developed, the researchers found that nearly 50 of those drugs had unfound anti-cancer properties. Also found in the studies were novel drug targets and mechanisms, which suggested that an innovative method of accelerating the development of new cancer drugs is the repurposing existing drugs.
"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 study researcher Todd Golub from Harvard University in the US.
Accidental stumblings
The study, published in the journal Nature Cancer, 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).
Historically, scientists have stumbled upon new uses for a few existing medicines, such as the discovery of aspirin's cardiovascular benefits. "We created the repurposing hub to enable researchers to make these kinds of serendipitous discoveries in a more deliberate way," said study first author Steven Corsello, from Dana-Farber Cancer Institute and founder of the Drug Repurposing Hub. The researchers tested all the compounds in the Drug Repurposing Hub on 578 human cancer cell lines from the Broad's Cancer Cell Line Encyclopedia (CCLE).
Some drugs killed cancer in unexpected ways
Using a molecular barcoding method known as PRISM, which was developed in the Golub lab, 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. Some of the compounds killed cancer cells in unexpected ways. "Most existing cancer drugs work by blocking proteins, but we're finding that compounds can act through other mechanisms," said Corsello.
Nearly fifty drugs identified
Some of the four-dozen drugs researchers identified appear to act not by inhibiting a protein but 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 -- a previously unknown mechanism for some of these drugs.
These unexpected drug mechanisms were easier to find using the study's cell-based approach, which measures cell survival, than through traditional non-cell-based high-throughput screening methods, Corsello said.
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.
