The anti-cancer drugs of the future may also come from the past. And the identification of previously undetected activity in molecules already in use could also have another repercussion: the discovery of mechanisms of action and targets that have been never been identified until now.
This type of study, which has been called repositioning (as it is based on the repositioning of already-approved drugs for uses that differ from their original purposes) has always been serendipitous in the field of cancer and linked to the specific research of individual laboratories or centers.
Now, however, experts from the “Broad Institute of MIT and Harvard” and the Dana-Farber Cancer Institute in Boston have worked systematically through the data stored in a large archive managed by the Broad Institute itself, which collects a broad range of information on 6000 drugs already in use. The researchers examined the anticancer activity of these drugs, achieving significant results.
As reported in the scientific journal Nature Cancer, the examination of more than 4500 old medicines, approved for the treatment of illnesses such as arthritis, diabetes, inflammation, hypercholesterolemia and other diseases, in fact led to the identification of around fifty molecules that have a powerful effect on fighting different types of cancer (such as cancer of the colon, lung cancer and other types of cancer). This result was achieved by testing the drugs on 578 cultured human cancer cell lines (i.e. tumors grown in test tubes).
Now, of course, new, wider, tests are to be conducted directly on humans. However, if the results are validated further, the approval process for these drugs (which are often low-cost) may be faster than usual, seeing that these molecules have already passed the required tests for entering the market.
As we have said, the researchers also tried to understand how these “old” drugs affected tumors, and they discovered that in several cases the effects were different from what was known up till now: for example, it is the activation of several proteins that messes up – so to speak – the systems that tumors need to develop, rather than the suppression of certain molecules found in cancer cells (the usual way that many anti-cancer drugs work).
In another case, a drug used to treat arthritis in dogs, called tepoxalin, demonstrated its ability to fight cancer by hitting a yet unknown target linked to the protein MDR1 (a protein that, when produced in quantities above the norm, creates a resistance to chemotherapy drugs).
Finally, a compound containing vanadium, designed to treat diabetes, proved effective in cancer cells that express a protein that transports sulphate, known as SLC26A2: all these paths are to be studied in more depth.