Harvard University scientists have discovered a fundamental mechanism of tumour growth, a breakthrough that may lead to more effective and less toxic treatments for cancer.
Indeed, two studies, published today in the journal Nature, may lead researchers to a potential “magic bullet” drug, that could attack many different forms of the disease, a top Canadian cancer expert says.
“This (research will present) one of the cancer (drug) targets that potentially could hit a whole variety of cancers. And there aren’t very many (drugs) like that,” says Philip Branton, head of cancer research with the Canadian Institutes of Health Research.
The twin Harvard studies show that cancer cells switch on the same sugar metabolizing enzymes as those found in fetal cells, explaining for the first time why tumours are able to grow so rapidly.
Like fetal cells, whose main job is to grow and divide to make a baby in just nine months, tumour cells grow and proliferate much more rapidly than normal adult tissues.
And to do so, both cancer and embryonic cells need to utilize energy, derived from sugary fuels, differently than their normal adult counterparts, Harvard biologist Lewis Cantley, the senior study author on both papers, said.
It’s been known for almost eight decades that tumour cells metabolize – or create energy from nutrients – at a much different rate than normal cells. This is the Warburg effect. What was unclear, says Cantley, was how they did this and whether or not the altered metabolic process was essential to tumour growth.
In the studies, scientists at the Harvard Medical School and Boston’s Beth Israel Deaconess Medical Centre showed that an enzyme that breaks down sugars in adult cells was switched to its embryonic version in cancer cells. Known as pyruvate kinase, the enzyme has an adult version, called M1 and a fetal version, M2.
“What our papers show is the embryonic form (M2) is designed to use glucose to make cells grow … the glucose gets incorporated into making DNA, RNA, proteins, lipids. It’s made into the cell building blocks,” Cantley says. “An adult cell is no longer growing so it uses glucose for energy.”
Branton says the study represents a significant breakthrough in cancer research. “It’s a major advance in understanding one of the oldest enigmas of cancer, which is the Warburg effect,” he says.
Critically, the Nature studies show that without the M2 version of the enzyme, tumour growth is slowed or outright halted. To show this the researchers genetically knocked out the ability to create M2 in several forms of human cancer cells, transplanting an M1 production component instead.
“We demonstrated that if you replaced the M2 the tumour cell has with the adult M1 form and implant that into a mouse, if fails to grow,” Cantley says.
He says the importance of M2 enzyme in tumour growth will make it an intriguing new target for better, safer cancer drugs.
Because normal adult tissues use the M1 version, a drug that specifically targeted M2 would, presumably, have minimal effect on anything outside of the tumour itself, Cantley says.
“That’s why we’re very excited about this as major tissues like the heart, the brain, the liver, those tissues don’t use the M2 form at all,” he says.
“If you had a (drug) that hit M2 … that should have no effect on the heart or the brain or the liver, which are the tissues you most worry about with cancer drugs. It should be far less toxic than … current chemotherapy.”
Branton, however, cautions that a drug that would specifically