Simple, cheap drug holds cancer treatment promise
Published Wednesday, May 12, 2010 9:48PM EDT
An inexpensive drug already in use for other diseases might hold the key to a completely new way of treating cancers -- not by killing off cancer cells, but by simply reprogramming them.
The finding comes from some exciting Canadian research on patients with brain tumours. The study found that DCA -- or dichloroacetate -- can shrink the tumours by altering a cancer cell's metabolism.
While the study was small -- just five patients were studied -- the researchers say their findings are "proof in principle" that the treatment approach works.
Cancer cells are notoriously resistant to death, because of their tendency to kick their own cell metabolism into high gear and gobble up lots of nutrients. Cancer cells can also suppress mitochondria, which are the tiny powerhouses inside cells that convert food into energy and which can kill off its own host cell if it demands too much energy.
Back in 2007, Dr. Evangelos Michelakis, a professor at the University of Alberta department of medicine, discovered along with and colleagues that DCA might help slow cancer growth.
DCA is a common compound that has been used for years to treat children with inborn mitochondrial diseases, by "boosting" and normalizing their mitochondria. Michelakis wondered whether DCA could also help repair the damage cancer causes to mitochondria.
In test of lab rats, his team found that DCA did help reprogram cancer cell mitochondria, thereby stunting the growth of lung, breast and brain tumours in both rats and in human tissue samples.
What's more, the drug left healthy cells healthy, unlike other cancer treatments such as chemotherapy and radiation. Because healthy cells don't have the same mitochondrial changes as cancer cells, the DCA left them unchanged.
Now, Michelakis has led a team to test the effects of DCA on patients with glioblastomas, a highly aggressive type of brain cancer that has few other treatments.
They treated five glioblastoma patients with DCA, seeking only to find out if the compound was safe and reacted as it should. Even though this trial was not meant to determine whether compound slowed the cancer, in fact, they found it did.
Brain imaging scans revealed that in four of the patients, no further cancer growth was seen for 15 months after initial treatment. In three of the patients, the tumours actually shrank.
Follow-up studies on cells taken from these patients showed that the DCA helped normalize cancer mitochondria to they could kill off cancer cells, along with other anti-tumour effects. What's more, none of the patients reported significant side effects when taking DCA at the level prescribed.
"We showed that DCA was killing the brain cancer cells," Michelakis told CTV News. "But more importantly, we had evidence that DCA might be doing the same thing in cancer stem cells, which are the mother of all cancer cells."
A 'new frontier' for cancer treatment
Michelakis say he's delighted with the results, which are published in the journal, Science Translational Medicine.
"It's now clear that targeting metabolism for cancer might be a new frontier for cancer," he said.
Dr. Joseph Megyesi, a neurosurgeon who is the chair of the board of directors for the Brain Tumour Foundation of Canada, expressed cautious optimism about the study, noting that false hopes have been raised before.
"There have been other new ways of approaching glioblastoma that when tested over longer period of time didn't turn out to be as good as initially suggested," he told CTV.
But Megyesi also said that patients "should be cautiously optimistic that this potential treatment may be effective down the road."
Researchers' biggest challenge: no industry support
Still, he said, if DCA is shown in further studies to be effective, the fact that it is already being used to treat mitochondrial diseases would make it easier for it to be approved for a new use.
Michelakis notes that all of the studies they've undertaken thus far on DCA have come with the support of the University of Alberta and public donations. That's in part because DCA is a commonly available compound that is not patented or owned by any drug firm. Pharmaceutical companies have not been interested in funding further research on DCA since the treatment won't make them a profit.
"That was the biggest challenge in the beginning: no industry support, no clinical applications," Michelakis said.
"We showed that, yes, you can take a generic drug, and if you have the right support, from the university and from the health authority and you have the generous support of donors and funding agencies, you can make it happen," he said.
He also notes that similar studies will soon start on the use of DCA for treating breast cancer, and could be extended to other cancers, too.
The University of Alberta continues to solicit funds to advance the research on DCA. Anyone who would like to donate to the university's DCA Cancer Research Fund can do so online, or by contacting the university's Faculty of Medicine.
With a report from CTV's Avis Favaro and Elizabeth St. Philip