Dozens of non oncology drugs can kill cancer cells, Drugs for diabetes, inflammation, alcoholism and even for treating arthritis in dogs can also kill cancer cells in the laboratory.
The researchers systematically analyzed thousands of drugs that had been developed and found nearly 50 who had not previously recognized cancer activity.
The surprising findings, which also reveal new mechanisms and targets for drugs, suggest possible ways to accelerate the development of new cancer drugs or reassign existing cancer drugs. the Dozens of non oncology drugs can kill cancer cells.
This is the largest study to date using the Large Drug Center, a collection that currently includes more than 6,000 FDA-approved drugs and compounds or has been proven safe in clinical trials (at the time of the study, the center included 4,518 drugs)).
The study is also the first time researchers have tested an entire collection of drugs that are mostly cancer-free for their anti-cancer abilities.
In the past, scientists have developed new applications for several existing drugs, such as discovering the cardiovascular benefits of aspirin. The researchers tested all drugs at the drug center found in 578 human cancer cell lines from the Broad Encyclopedia of Cancer Cells (CCLE).
Using a molecular barcode method known as PRISM developed in the Golub laboratory, the researchers labeled each cell line with a DNA barcode so that they could bind many cell lines in each plate and quickly carry out larger experiments.
The team then exposed each set of barcode cells to compounds from the library to be changed and measured the survival rate of cancer cells.
They found nearly 50 non-cancer drugs – including those originally designed to lower cholesterol or reduce inflammation – which kill some cancer cells while leaving others alone. Some compounds unexpectedly kill cancer cells. Most existing cancer drugs block proteins, but we found that these compounds can work through other mechanisms.
For example, the team found that nearly a dozen non-cancer drugs kill cancer cells that express a protein called PDE3A, thus stabilizing the interaction between PDE3A and another protein called SLFN12, a mechanism previously unknown for some of these drugs.
This unexpected mechanism of action is easier to find with cell-based tests that measure cell survival compared to conventional non-cell high screening methods. Most of the non-cancer drugs that kill cancer cells in this study interact with previously unknown molecular targets.
For example, the anti-inflammatory drug tepoxaline, which was originally developed for use in humans but is approved for the treatment of osteoarthritis in dogs, kills cancer cells with an unknown target in cells expressing excessive MDR1 protein, which normally causes resistance to chemotherapy drugs.
Researchers can also predict whether certain drugs can kill cell lines by examining cell line genome features, such as mutation and methylation rates, contained in the CCLE database. This shows that one day these traits can be used as biomarkers to identify patients who are most likely to benefit from certain drugs.
For example, drugs against alcohol-dependent disulfiram (antabuse) kill cell lines that carry mutations that cause the depletion of the metallothionein protein. Vanadium-containing compounds originally developed to treat diabetes kill cancer cells expressing SLC26A2 sulfate transporters.
The genome characteristic gave us an initial hypothesis about how the drug might work, and we could then return to laboratory tests. Our understanding of how these drugs kill cancer cells gives us a starting point for developing new therapies.
The researchers hope to study the compounds from the library that transform in more cancer cell lines and to develop a hub to include more compounds that have been tested in humans.