Why wait for Serendipity? Screening Reveals Existing Drugs with Anticancer Properties

From the discovery of penicillin and X-rays to the invention of pacemakers, serendipity has ever been the scientist’s friend. Every once in a while, a pre-existing drug is found to have unforeseen applications in treatment of other diseases. In this way, a number of anti-cancer drugs have been discovered.

In this Nature Cancer study, researchers decided to actively look for such drugs, using a technique called PRISM (profiling relative inhibition simultaneously in mixtures). They screened thousands of existing drugs, and were surprised to find as many as 49 compounds that showed previously unrecognised anticancer activity. These could be used to develop new anticancer therapies, or potentially be directly re-purposed should they prove effective enough.

The prospect of screening large numbers of pre-existing drugs for new applications is enticing. In addition to being cheaper than developing an entirely new therapy, the compound’s safety in humans would already have been confirmed in previous drug trials.

The team’s newly published study marks the first time that the entire collection of mostly noncancer drugs has been screened for anticancer activity. By using the PRISM molecular barcoding technology, which was developed in the Golub lab, the researchers were able to test all the compounds in the Drug Repurposing Hub on 578 human cancer cell lines from the Broad’s Cancer Cell Line Encyclopedia (CCLE). Each cell line was tagged with a DNA barcode, which allowed them to pool several cell lines together, which made it possible to conduct a much larger overall 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. “Cancer cell lines are labeled with unique DNA sequences, thereby allowing barcoded cell lines to be pooled with relative barcode abundance serving as a surrogate for cellular viability,” they wrote.

The screen identified 49 noncancer drugs that were active against some types of cancer cells, a number of which killed the 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. Some of the drugs with anticancer activity appeared to act not by activating, rather than inhibiting a protein, or by stabilizing a protein-protein interaction. These unexpected drug mechanisms were easier to find using the cell-based approach that measures cell survival, than through traditional non-cell-based high-throughput screening methods, Corsello said.

https://www.genengnews.com/news/anticancer-activity-discovered-in-dozens-of-existing-noncancer-drugs/