October 21, 2018

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New weapon against cancer?

Sperm cells and cancer are indeed odd bedfellows. Rarely are the two mentioned in the same breath. Yet a top cancer researcher out of Israel may change that after finding a key enzyme in metastatic cancers — often the most aggressive form of the disease — that’s only found under normal circumstances in sperm cells.

Dr. Uri Nir is the director of the Nano Medicine Center at the Institute of Nanotechnology and Advanced Materials (BINA), and dean of the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University in Israel.

It’s a mouthful of titles for sure.

But what’s important about his role is for the past several years he has been searching for a silver bullet to cure metastatic cancers.

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Sperm cells and cancer are indeed odd bedfellows. Rarely are the two mentioned in the same breath. Yet a top cancer researcher out of Israel may change that after finding a key enzyme in metastatic cancers — often the most aggressive form of the disease — that’s only found under normal circumstances in sperm cells.

Dr. Uri Nir is the director of the Nano Medicine Center at the Institute of Nanotechnology and Advanced Materials (BINA), and dean of the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University in Israel.

It’s a mouthful of titles for sure.

But what’s important about his role is for the past several years he has been searching for a silver bullet to cure metastatic cancers.

"The metastatic phase is really the challenging part of the disease," he says, because migrating cells are often resistant to chemotherapy and to many other new treatments.

Yet the basic science researcher believes his team has not only discovered why metastatic cancer is so difficult to treat. He has also developed a compound — a potential drug therapy — now in the process of being financed by a major pharmaceutical company in the United States after it proved very effective treating mice.

And next month Winnipeggers can hear more about Nir’s work when he is in town to speak with the public. Sponsored by the Winnipeg Jewish Business Council, Nir is scheduled to speak at three events Oct. 4 (see fact box).

For anyone curious about the biology of cancer or, more importantly, wondering what new treatments might be in the pipeline to battle the disease, hearing Nir speak is worthwhile.

In an interview with the Free Press, Nir briefly discussed the basics of the promising potential drug therapy he developed, a synthetic compound called EMIZIL (its scientific name is E260).

The legwork for his "Eureka!" moment involved a painstaking search for a weakness in metastatic cancer cells, which are often highly resistant to chemotherapy and radiation therapy. While breakthroughs have been made with new immunotherapies, by which the immune system is coaxed into attacking cancer cells, it has only proven effective in about 30 per cent of patients, for only a few types of cancers, Nir says.

The reason metastatic cells, which often enter the bloodstream from the primary cancer site to migrate elsewhere in the body to start new tumours, are so difficult to treat is because they are roughest and toughest of all malignant cells.

"Fortunately, the metastatic phase for these cells is relatively inefficient," he says. Cut off from the blood supply providing the primary tumour with nutrients and oxygen, most don’t survive the trip.

But those that do tend to thrive. So Nir sought to find why these cells survive in harsh environments.

"We argued that if metastatic cancer cells are able to survive under really abnormal and very extreme stress conditions, they should be able to produce energy under very extreme conditions."

That led him to examine cancer cells’ mitochondria.

In all cells, mitochondria are the "power stations" that provide energy for cellular functions.

"It is known the mitochondria are reprogrammed in cancer cells to produce energy in a modified way," he explains.

What his team discovered is an enzyme unique to cancer cells found in the mitochondria, allowing these power stations to produce energy in environments without oxygen and nutrients. Called FerT, this protein is not present in any healthy human cell except one.

"We found it only in the mitochondria of sperm cells… even though the gene (that controls its production) is present in women and embryos (but not expressed)."

Cancer may be an awful disease, but you have to admire its ingenuity when it comes to commandeering our genetic code for its own diabolical means.

And that’s exactly what it does here, activating a gene silent in all human cells (unless it’s a sperm cell) to its own advantage.

What this gene does normally when activated is allow production of the enzyme, permitting sperm cells to survive in a completely foreign environment on their journey to fertilize an egg. In cancer cells, the same gene gets expressed facilitating their destructive voyage to parts unknown in the body.

Of course finding a possible Achilles heel in cancer cells is one thing — and fairly big thing at that. Developing an agent is quite another. Yet that’s what Nir’s team did, their findings published in a 2017 article in Nature Communications.

EMIZIL "not only destroys the enzyme," he says. "It really destroys the whole structure of the mitochondria in cancer cells, but not in normal cells."

So far in tests on mice with pancreatic, lung and breast cancers, to name a few, the agent "uniquely kills all metastatic cells we have tested."

It also caused no significant side effects, completely curing the mice, he adds.

The next step is raising tens of millions of dollars for clinical testing on humans. Nir says his hope is Phase 1 clinical trials to test the drug’s safety in humans will begin within the next 20 months.

"This is a whole different arena" of cancer treatment, he adds.

"Our approach belongs to the targeting of reprogrammed metabolic pathways in cancer cells."

Basically, the idea is to starve cancer cells of the energy they need to spread.

Nir notes other drugs have come to market targeting the mitochondria in cancer cells, but they are used mostly for leukemia and only benefit a certain number of patients.

Nir’s hope is that drug will be a panacea treatment for the most aggressive forms of disease.

While seemingly a major breakthrough, one thing to keep in mind is the experimental therapy remains in its early stages; even if it is effective in humans, its use as a treatment in Manitoba is likely years away.

"There is still a lot to do," Nir cautions.

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History

Updated on Wednesday, September 26, 2018 at 10:19 AM CDT: Adds link to event

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