Drug review finds hidden options
A lab set up to re-test old drugs has found dozens of potential new cancer treatments.
Recent tests of thousands of medicines on hundreds of cancer cell lines has uncovered new tricks for many old drugs.
The Drug Repurposing Hub at the Broad Institute in the US holds over 6,000 drugs and compounds that are either FDA-approved or have been proven safe in clinical trials.
In a new study, researchers screened the entire collection of mostly non-cancer drugs for their anti-cancer capabilities.
It found nearly 50 that have previously unrecognised anti-cancer 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.
“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, a researcher and professor of paediatrics at Harvard Medical School.
Historically, scientists have made some important 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.
Several of the 50 non-cancer drugs — including those initially developed to lower cholesterol or reduce inflammation — were found to kill 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 Dr Corsello.
Some of the four-dozen drugs he and his colleagues identified appear to act not by inhibiting a protein but by activating a protein or stabilising 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 stabilising the interaction between PDE3A and another protein called SLFN12 — a previously unknown mechanism for some of these drugs.
Most of the non-oncology drugs that killed cancer cells in the study did so by interacting with a previously unrecognised 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 hope to study the repurposing library compounds in more cancer cell lines and to grow the hub to include even more compounds that have been tested in humans.
The team will also continue to analyse the trove of data from this study, which have been shared openly with the scientific community, to better understand what’s driving the compounds’ selective activity.
“This is a great initial dataset, but certainly there will be a great benefit to expanding this approach in the future,” said Dr Corsello.