Non-Cancer Drugs Identified to Kill Cancer Cells
Scientists at the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have found that drugs used for inflammation, diabetes, alcoholism, and arthritis also have anti-cancer properties. Published in Nature Cancer, this is the first study to screen an entire collection of mostly non-cancer drugs to see if they can kill cancer cells. The new findings could help identify novel mechanisms and targets to repurpose drugs or create new ones to help combat the disease.
As well as being the first study of its kind, it’s also the largest. The researchers used drugs from the Broad’s Drug Repurposing Hub, a collection of more than 4,000 drugs and compounds that were proven safe in clinical trials or FDA-approved.
These drugs were analysed on 578 human cancer cell lines from the Broad’s Cancer Cell Line Encyclopaedia (CCLE). They employed a molecular barcoding method called PRISM which tagged each cell line with a DNA barcode and allowed the cell lines to be pooled together in one dish. Each pool of barcoded cells was then exposed to a drug, and the survival rate of the cancer cells was measured.
Nearly 50 non-cancer drugs were found to kill cancer cells but leave healthy cells thriving. The researchers found that some cancer cells were killed in unexpected ways, shedding light on novel drug mechanisms and potential targets. Nearly a dozen drugs killed cancer cells that express a protein called PDE3A through stabilising interactions between PDE3A and another protein SLFN12. This was a previously unknown mechanism for some of these drugs.
An anti-inflammatory drug called tepoxalin was found to kill cancer cells with an overexpression of the protein MDR1, one that commonly drives resistance to chemotherapy drugs through an unknown route.
The cancer cells from the CCLE each had their own genomic features, and the researchers could use this to predict which drugs could kill each cancer cell line.
Antabuse, an alcohol dependence drug, could kill cancer cell lines with mutations causing a depletion of metallothionein proteins. Drugs containing vanadium, originally used in treating diabetes, could kill cancer cells expressing SLC26A2, a sulphate transporter. This knowledge could be extremely useful in determining which patients may benefit the most from certain drugs.
The researchers aim to study the effects of even more drugs on different cancer cell lines to fully understand what mechanisms are at play, and potentially repurpose drugs or develop new cancer drugs that could help combat the disease.