Low-oxygen study offers hope for anti-cancer drug

Don Butler, Postmedia News · May 7, 2012 | Last Updated: May 7, 2012 3:01 AM ET

OTTAWA – A team of University of Ottawa researchers has solved the mystery of how our bodies adapt to low-oxygen environments, raising the prospect that life-threatening conditions such as cancer, stroke and heart disease could someday be successfully treated using a simple, antibiotic-like drug.

The team’s findings were published Sunday in Nature, the world’s leading scientific journal.

“It’s a tremendously important discovery in understanding how life without oxygen works,” said Dr. Stephen Lee, a professor in the university’s Department of Cellular and Molecular Medicine, whose laboratory did the groundbreaking research.

Scientists have known for decades that in the presence of oxygen, cells make proteins – the building blocks of life – using a process called protein synthesis.  But how they do so in conditions of limited oxygen had remained a mystery.

Dr. Lee’s team found there’s an oxygen-regulated switch in the protein synthesis machinery, a “very novel and unexpected way of synthesizing proteins,” Dr. Lee said. “It’s very different.”

The discovery explains, for the first time, how mountain climbers and highland Tibetans are able to adapt and function in environments that would kill or sicken most people.

The implications for cancer treatment, though still speculative, are potentially huge.  Dr. Lee’s team discovered that cancer cells proliferate by using the same protein synthesis machinery the body employs to deal with low levels of oxygen.

Cancer cells “utilize that way of producing proteins without oxygen, even if oxygen is present,” Dr. Lee said. “They hijack that system and that drives their proliferation.”

If the cancer cells use the low-oxygen machinery to spread, he said, “we can develop an antibiotic against that protein synthesis machinery. It’s as easy as that. And it’s working very well.”

The comparison to antibiotics is apt, Dr. Lee said.  Drugs such as penicillin and tetracycline kill bacteria by preventing them from synthesizing proteins.  A future cancer drug would “work in a similar fashion,” Dr. Lee said, using the low-oxygen machinery to block protein synthesis in cancer cells.

That should make it “very easy to kill cancer cells,” he said.  “We’re doing it right now in the lab. We just need to develop a drug now, which is not trivial, but it’s not that difficult, either.”

The sort of cancer treatment imagined by Dr. Lee would be a radical departure from the current approach, which relies on toxic doses of chemotherapy and radiation.

“The major dogma right now is that we have to attack cancer cells using very specific drugs that target very specific molecules” said Dr. Lee.

“If we are right, this is the first systemic difference between a normal and a cancer cell. Rather than targeting some molecule, we would just strip the cancer apart by preventing it from making the building blocks”.

Dr. Lee had not originally planned to include the reference to cancer treatment in the Nature article “because we thought it was too speculative and Nature is a very conservative journal.  But they really asked us to point the possibility out”.

“They liked it.  I like it.  We have data that suggests we’re right.  We just need to prove it more and convince some chemists to start working on it”.