'Suicide molecule' could lead to fail-safe cancer therapy, scientists say

A "suicide molecule" that forces tumours to self-destruct could open the door to fail-safe cancer therapy, scientists believe.

In laboratory tests, cancer cells treated with the molecules were unable to develop resistance to them.

The super-weapon simultaneously eliminates multiple genes that cancers need to grow and spread.

Team leader Professor Marcus Peter, from Northwestern University in Chicago, US, said: "It's like committing suicide by stabbing yourself, shooting yourself and jumping off a building all at the same time. You cannot survive.

"This could be a major breakthrough."

The small double-stranded molecules of RNA - a genetic cousin of DNA - appear to trigger an ancient anti-cancer "kill switch" present in all cells, said the scientists.

Prof. Peter's team discovered instructions for making the molecules buried in the human genetic code, ending an eight-year search.

"We think this is how multicellular organisms eliminated cancer before the development of the adaptive immune system, which is about 500 million years old," said the professor. "It could be a fail safe that forces rogue cells to commit suicide.

"We believe it is active in every cell protecting us from cancer."

The hunt for the elusive molecules was based on the premise that if they did not exist, complex life on Earth would have been wiped out by cancer long ago. But the researchers knew they would be hard to find.

"It was a needle in a haystack," said Prof. Peter.

The molecules belong to a class of small interfering RNAs (siRNAs) that have the effect of silencing certain genes so their instructions cannot be read.

They are derived from special sequences of DNA embedded throughout the human genome, or genetic code book, the researchers reported in the journal Oncotarget.

Each sequence contains the "plans" for one of the secret weapons, an siRNA that targets multiple cancer survival genes.

Removing the genes activates programmed death pathways that causes the cancer cell to destroy itself - a mechanism dubbed DISE (Death Induced by Survival gene Elimination) by the scientists.

In mice with human ovarian cancer, the RNA molecules strongly suppressed tumour growth with no side effects. Importantly, the tumours could not develop resistance against the attack.

Patients with advanced solid cancers, such as those of the brain, lungs or ovaries, have seen little improvement in survival because the drugs used to treat them do not remain effective, said Prof. Peter.

"The problem is cancer cells are so diverse that even though the drugs, designed to target single cancer driving genes, often initially are effective, they eventually stop working and patients succumb to the disease," he said.

"If you had an aggressive, metastasising (spreading) form of the disease 50 years ago, you were busted back then and you are still busted today.

"Improvements are often due to better detection methods and not to better treatments."

Immunotherapy treatment had been partially successful because it is geared towards activating one of nature's anti-cancer mechanisms, said Prof. Peter.

However, few cancers responded to immunotherapy and only a few patients benefited.

He added: "Our research may be tapping into one of nature's original kill switches, and we hope the impact will affect many cancers."


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