SOME new cancer drugs emerge through better understanding of how the disease develops. Others work in ways we do not understand, and so give us fresh insight. It is rare to find a drug that sweeps away decades of assumptions and reveals a radical approach to treating all forms of the disease.
The drug is a simple, small molecule called dichloroacetate (DCA). Research in Canada led by Evangelos Michelakis of the University of Alberta has shown that it has promising anti-cancer properties. That鈥檚 not all. The drug鈥檚 mode of action is also generating excitement.
In 1930, biochemist Otto Warburg proposed that cells turn cancerous by changing the way they generate energy. Normally, cells rely on specialised organelles called mitochondria to supply their energy. Cancer cells switch to a process called glycolysis, which takes place in the body of the cell. It is an inefficient process, used by many bacteria 鈥� and marathon runners 鈥� when oxygen is in short supply.
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Curiously, Warburg found that cancer cells continue to use glycolysis even when oxygen is plentiful. He argued that this fact, now called the Warburg effect, was a defining property of cancer cells. However, the idea did not catch on, not least because another famous biochemist, Hans Krebs, said the Warburg effect was only a symptom of cancer, not its primary cause. This scepticism was reinforced by the belief that cancer cells only switch to glycolysis because their mitochondria fail.
Enter DCA, which has been used for years to treat people with mitochondrial disease. The drug boosts the ability of mitochondria to generate energy. When given to cancer cells, it did the same: it seems that mitochondria in cancer cells are not irreparably damaged after all. What鈥檚 more, functioning mitochondria help to kill off these aberrant cells (see 鈥淐heap, safe drug kills most cancers鈥�).
When Michelakis tested the drug on cancer cells in culture, they died. When he gave it to rats with human tumours, the tumours shrank. It appears Warburg may well have been right that the switch to glycolysis is more than just a symptom of cancerous cells.
Best of all, DCA looks like a potential anti-cancer agent. It is cheap, does not appear to affect normal cells, we know its side effects, and it should work on all cancers. But there鈥檚 a hitch: it is an old drug and so cannot be patented. No pharmaceutical company is likely to fund costly clinical trials without some exclusive rights to make the drug.
This is not a new problem. Many drugs are left on the shelf because companies cannot make lots of money from them. It has happened with drugs for diseases that affect mainly poor people in developing countries, such as TB, though there are now an increasing number of partnerships between governments, charities and commercial companies to deal with these cases. Cancer, by contrast, is chiefly a disease of the rich, and testing DCA will need a one-off effort.
It is a safe bet that drug companies will be falling over themselves to find patentable compounds with a similar action to DCA. Any of these reaching the market will be hugely expensive. It would be a scandal if a cheap alternative with such astonishing potential were not given a chance simply because it won鈥檛 turn a big enough profit.
