Almost 50 Non-Oncology Drugs Found to Kill Cancer Cells
Almost 50 non-oncology drugs were found to have previously unrecognized anti-cancer properties in a new research of Scientists at the Broad Institute of MIT and Harvard.
The drugs ranged from treatments for diabetes, inflammation, alcoholism and arthritis in dogs, reports BioSpace.com.
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.
The research was published in the journal Nature Cancer.
Scientists tested about 4,518 drugs on 578 human cancer cell lines
The research leveraged the Broad’s Drug Repurposing Hub. This Hub is made up of more than 6,000 existing drugs and molecules the U.S. Food and Drug Administration (FDA) has either already approved or have been shown to be safe in clinical trials. At the time the group conducted their study, there were 4,518 compounds in the Hub.
The investigators evaluated all the molecules in the Drug Repurposing Hub on 578 human cancer cell lines from the Broad’s Cancer Cell Line Encyclopedia (CCLE). They leveraged a molecular barcoding technique called PRISM, also developed in the Golub lab, that allowed the team to tag each cell line with a DNA barcode. This let them pool several cell lines together in each Petri dish, allowing them to run a larger experiment faster. They then exposed each pool of barcoded cells to a single drug and measured the survival rate of the cancer cells.
Unexpectedly, they found almost 50 non-cancer drugs killed some cancer cells. They also found that some of the drugs killed cancer in unusual ways.
Unknown mechanism found
Most existing cancer drugs work by blocking proteins, but we’re finding that compounds can act through other mechanisms,”said Steven Corsello, an oncologist at Dana-Farber Cancer Institute, founder of the Drug Repurposing Hub, member of the Golub lab and first author of the study.
For example, some of the drugs activated a protein or stabilized a protein-protein interaction. Almost a dozen of the non-cancer drugs killed cancer cells expressing the PDE3A protein by stabilizing the PDE3A and SLFN12 protein interaction. This was an unknown mechanism up to now.
Many of the drugs killed cancer cells by interacting with a previously unrecognized molecular target. One example is the drug tepoxalin, used to treat osteoarthritis in dogs. But the drug killed cancer cells by interacting with an unknown target in cancer cells that overexpress the MDR1 protein, which is linked to resistance to chemotherapy drugs.
The researchers were further able to evaluate the cell line’s genomic features and predict which drugs could kill each cell line. Those genomic features included mutations and methylations levels, which were available in the CCLE database.