U of A finds promising cancer drug

Generic drug needs funding to begin human trials

ROBIN COLLUM THE GATEWAY (UNIVERSITY OF ALBERTA)

ALBERTA (CUP) — Researchers at the University of Alberta have opened a new door in cancer treatment by researching an alternative use of a drug that’s been around to treat other diseases for decades.

In a paper released this month in the medical journal Cancer Cell, a group of scientists from the U of A and the University of Ottawa announced that a molecule previously used to treat certain genetic conditions has been shown to kill cancer cells and shrink tumours in lab rats.

The group, led by U of A’s Dr. Evangelos Michelakis, has shown that the generic drug dichloroacetate (DCA) induces death in cancer cells by improving mitochondrial function in the cells. Mitochondria, the major energy-producing units in cells, are also in charge of regulating cell death. Scientists have known since the 1930s that mitochondria in cancer cells don’t work properly, but it was thought that this was an irreversible result of the cancer.

Until now, no one had discovered that the mitochondria could be restored to their previous function.

“The development of cancer is associated with mitochondrial dysfunction,” explained Dr. Sebastien Bonnet, the U of A post-doctoral student who was the first author of the paper and conducted most of the experiments. “By restoring the mitochondrial function with DCA we were able to decrease the tumour size, kill the cancer cells and block the growth of cancer.”

“When we inject the cancer cells into rats, we see the first effect within a week. It’s a slow process, but the tumour size decreases steadily, and goes like that as long as we’ve been testing.”

DCA has been used since the 1970s to treat other conditions and diseases, but its use hadn’t been considered for cancer treatment until now.

“What’s so intriguing about this work is that it addresses one of the oldest observations in the study of cancer, and takes advantage of this research by using a drug that’s already in the clinic,” said Dr. Philip Branton, scientific director of the Institute of Cancer Research, one of the Canadian Institutes for Health Research, which provided much of this research’s funding. “DCA is already used therapeutically, and has been shown to be safe.”

So far, all of the DCA experiments have been on laboratory rats injected with cancer cells from human lung, breast or brain tumours. It’s still unknown whether the same results will appear when the drug is tested on humans, because this is the first time that mitochondria have been targeted in cancer treatment.

“There are three possibilities for how it could work on humans,” Bonnet explained. “DCA is going to kill all the tumour and it won’t come back; or DCA will at some point stop working and the tumour will be so small that we can easily take it out with simple surgery; or maybe DCA combined with other chemotherapy agents will kill the tumour. We have a lot of experiments still to do.”

Or, it could not work at all. Branton cautioned against people getting their hopes too high based on such preliminary results.

“I’ve had a whole bunch of people contact me, wanting to know about trials for their parents and for themselves,” he said. “But this is really early preclinical work. This is only one drug. There are dozens of good drugs around, and is this better than something else? I don’t know.”

The next step is to begin human trials — a long, complicated and expensive process. First, researchers must prove that a drug is safe, though that step won’t be as difficult with DCA. Then they begin testing for efficacy, experimenting on different types and stages of cancer with varying dosages of the drug.

“That stage is a million times harder,” Michelakis said. “You translate what you find in animals to human beings, and it’s far more difficult. If you do something in animals that never transfers to humans, it’s a big nothing; it’s big waste.”

An advantage for Michelakis and colleagues is that they will likely be able to skip traditional first-phase trials, because DCA already known to be safe drug. Unfortunately, DCA’s prior use causes another problem: no one wants to invest in it.

Before Michelakis’ group began their research, DCA was not under patent. And, since its makeup was generally known, a structural patent could not be filed. During the course of their research, Michelakis and another U of A doctor involved in the project, Dr. Stephen Archer, obtained a use patent. This type of patent, relating to the use of a drug rather than its manufacture, is difficult to defend. Investors are therefore wary of putting money into its development.

“If [a drug] is not properly patented, they could never get their money back, because anyone could then make the drug,” explained Dr. Branton. “A company might invest millions of dollars into clinical trials and then anyone could sell it.”

In order to move DCA into the clinical trials stage of development, the research group will probably have to rely on government and other nonprofit sources.

“We were looking for investors, and no one was interested,” Michelakis said. “That’s why we have government, that’s why we have groups like the CIHR, the National Cancer Institute, and other agencies and philanthropies. That’s why they’re there.”

So far, all of the DCA experiments have been on laboratory rats injected with cancer cells from human lung, breast, or brain tumours. It’s still unknown whether the same results will appear when the drug is tested on humans. Observers like Branton are particularly optimistic about the success of potential trials because DCA has been used on humans for so long.

“We know it’s probably safe, and we know it works on human cancer cell lines in animals, but we don’t know if it will work on human beings,” Michelakis said. “We also don’t know long-term effects.

We have a lot of experiments still to do.”