CJN Article: "HU Scientist Seeks to Starve Cancerous Tumours"

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CJN Article: HU Scientist Seeks to Starve Cancerous Tumours

Eli KeshetJERUSALEM —Driven by the ambition to discover an alternative to risky bypass surgery and a way to starve cancerous tumours, Hebrew University of Jerusalem professor Eli Keshet has spent the last two decades studying the vascular system and the mechanisms of blood vessel formation.

In June, during a six-day trip to Israel sponsored by the Canadian Friends of Hebrew University – a non-profit organization that promotes and raises funds for Hebrew U, with chapters from coast to coast – six Canadian journalists spent an afternoon with some of Israel’s brightest scientific minds.

One of the meetings was with Keshet, who spoke of his discovery that revealed a protein called VEGF, which initiates the formation of new blood vessels when older ones need to be bypassed because of an occlusion, or a blockage.

With this knowledge, Keshet is also working to understand how to inhibit the formation of blood vessels so as to starve cancerous tumours that rely on blood vessels for nourishment.

Keshet’s work has contributed to clinical trials of cancer-fighting drugs that neutralize a tumour’s ability to attract blood vessels from which it thrives.

“Our work concerns trying to gain more insight into how new blood vessels are made in the body. The notion is that once sufficient insights are made, maybe we can harness this knowledge in order to manipulate the vascular system at will,” Keshet said.

He said every organ and tissue in the body is no further away than one-tenth of a millimetre from a blood capillary so that it can secure an efficient exchange of blood cells.

When an artery becomes clogged, all the tissues that are serviced by these vessels are now suffering from an insufficient supply of oxygenated blood cells.

“In our vascular system, in a remarkable way, it can always sense that if there are not enough blood vessels in the area… it has a remarkable ability of self-rectifying itself to make more blood vessels in the area where you need to enforce the vascular supply,” Keshet said.

“The question is, how does the tissue know that it needs to make new blood vessels? The tissue knows because it’s experiencing hypoxia. The lack of oxygen is the signal for the trigger. Somehow, this factor, VEGF, is responsive to the lack of oxygen.”

He said that when tissue experiences hypoxia, it secretes VEGF and reacts on specific receptors that are found on the surface of blood vessels.

Although the body has a way of producing blood vessels to bypass blockages naturally, Keshet said, it often becomes a race against time.

“What would happen first? Would you lose a limb or suffer some major consequences, or would you [produce the vessels] in time [to avoid any damage]?”

When a blockage is detected, Keshet said, the common practice is for surgeons to use an existing artery or vein from another part of the body and connect it to the heart so that the blood can bypass the occlusion.

But the hope, he said, is that his research will lead to a way to trigger the body to create new blood vessels more efficiently where and when they are needed so as to avoid surgery.

“If we can implant, pharmacologically, some protein or a factor that induces the formation of new blood vessels – we are thinking about making our own bypasses instead of resorting to surgical bypasses,” Keshet said.

“This would be great, wouldn’t it? But the question, of course, is how you do it… How can we make it fast enough or efficient enough before [a patient] suffers an amputation or heart disease?”

Keshet said the protein responsible for triggering the formation of new blood vessels, VEGF, can be made artificially.

“We isolated the gene that makes the factor and we can implant it and we can produce tons of it. Producing the factor is not a problem. But the question is, how are we going to apply it?”

He said the factor is currently the subject of clinical trials to see the most effective way of administering it, whether by injection or by slow-release implants that release VEGF in a controlled way.

“Now people are trying to address the question of how to use it, to make sure it won’t be too much, how to secure it, make sure it works locally.”

Keshet said learning how to control the production of blood vessels could also help treat cancer. If medical specialists learn how to inhibit blood vessels from developing around cancerous tumours, the tumours could be starved of a blood supply and be kept from developing.

“The whole idea is, can we inhibit the angiogenic process so we can starve the tumour to death?… What you do is you inject something that would neutralize the VEGF activity… This is really straightforward thinking, and the nice thing is that it is working and it’s already in the clinic,” Keshet said.

He said the clinical trials are meant to discover how to improve the efficacy of this procedure, to reduce any side effects and try to anticipate whether a tumour could develop a resistance to the treatment.

“We want to see the mechanism of how tumours can escape this treatment by finding alternative ways of producing blood vessels because tumours always outsmart us… We want to outsmart the outsmarters.”

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