Drugs routinely prescribed for diabetes, inflammation, alcoholism – and even for treating arthritis in dogs – can also kill cancer cells in the laboratory, according to a new study that even caught the researchers by surprise.
The study – in which thousands of already developed drug compounds were systematically analysed for anti-cancer capability – discovered 49 medicines that not only neutralised cancer cells, but left healthy cells unharmed.
Some of these medicines were found to target cells in novel and surprising ways, potentially opening up new lines of attack against tumours. It also suggest “a possible way to accelerate the development of new cancer drugs or repurpose existing drugs to treat cancer drugs”.
More bang for your pharmaceutical buck
Central to this discovery was the relatively new and somewhat exciting Drug Repurposing Hub run by MIT’s Broad Institute.
The Hub is a repository for more than 6000 compounds – many of them on the market or approved by the US Federal Food & Drug Administration (FDA) – that may prove to be effective in treating conditions not originally targeted by researchers and developers.
The premise is simple: it can take a decade of lab work and clinical trials before a new drug comes on the market. Why not investigate if drugs already shown to be safe for human consumption can be repurposed?
The most famous example of a drug being dramatically repurposed is aspirin – it was initially developed as a painkiller, but was eventually discovered to be effective in preventing heart disease.
“We created the Repurposing Hub to enable researchers to make these kinds of serendipitous discoveries in a more deliberate way,” said founder Dr Steven Corsello, an oncologist at Dana-Farber Clinical Institute.
“In general, though, these kinds of discoveries are accidental.”
The study also marks the first time researchers screened the entire collection of mostly non-cancer drugs for their anti-cancer capabilities.
Scientists didn’t expect such a bonanza
For this new study, the researchers used a molecular barcoding technology called PRISM (profiling relative inhibition simultaneously in mixtures) to screen more 4000 existing drug compounds against 578 different types of 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,” Dr Todd Golub said, director of the Cancer Program at the Broad Institute, and professor of paediatrics at Harvard Medical School.
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,” Dr Corsello said.
Some of the drugs killed cancer cells not by inhibiting a protein, but by activating a protein or stabilising a protein-protein interaction.
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 over-express the protein MDR1, which commonly drives resistance to chemotherapy drugs.
This finding alone is worth getting excited about.
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 (short version: these regulate gene expression).
“This suggests that these features could one day be used as biomarkers to identify patients who will most likely benefit from certain drugs,” according to a statement from the scientists.
For example, the alcohol dependence drug disulfiram (Antabuse) killed cell lines carrying mutations that cause depletion of metallothionein proteins (not fully understood but they protect against oxidative stress).
“The genomic features gave us some initial hypotheses about how the drugs could be acting, which we can then take back to study in the lab,” Dr Corsello said.
“Our understanding of how these drugs kill cancer cells gives us a starting point for developing new therapies.”