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Cancer treatment that blocks cellular “protein factories” set to begin clinical trials

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July 10, 2012

A new cancer treatment targeting cellular 'protein factories' is set to begin clinical tri...

A new cancer treatment targeting cellular 'protein factories' is set to begin clinical trials (Image: Shutterstock)

Researchers at Melbourne’s Peter MacCallum (Peter Mac) Cancer Centre are set to begin clinical trials of a cancer treatment they say represents a major shift in molecular approaches to treating the disease. The treatment, which has proven successful in the lab against lymphoma and leukemia cells, targets the production of proteins within the heart of cancer cells, while leaving healthy cells relatively unaffected.

Ribosomes are a complex of molecules found within all living cells – including cancerous and healthy cells – that are responsible for the formation of proteins from individual amino acids. Associate Professor Ross Hannan, Co-Head of the Oncogenic Signalling and Growth Control Program at Peter Mac, says that the production of ribosomes, known as ribosome biogenesis, which occurs in both the cell cytoplasm and cell nucleus, was previously assumed to be a “housekeeping” operation that could not be targeted by anti-cancer drugs.

But Hannan, who has spent most of his research career investigating ribosome biogenesis and its importance to the biology of cancer cells, suspected otherwise.

“It was an unproven theory for many years, but I was confident we were on the right track, the key signs were there: when ribosome biogenesis is dysregulated, proteins are overproduced, creating rampant cell growth, a hallmark of cancer; and abnormalities of the nucleolus, the site of ribosome biogenesis, have been used as an indicator of cancer for over 100 years.”

The research team confirmed Hanna’s suspicions, finding that blocking this routine cellular process within cancer cells can selectively kill them, while leaving healthy cells unaffected.

“We’ve demonstrated that cancer cells are far more dependent on their ability to make ribosomes than normal cells, and therefore, much more vulnerable if these ‘protein factories’ come under attack,” said Hannan.

“When we blocked the enzyme responsible for producing the major ribosomal components in pre-clinical laboratory models, it set off a chain of events that killed lymphoma and leukaemia cells, but left normal, healthy cells unaffected,” added Professor Grant McArthur, Co-Head of the Cancer Therapeutics Program, who says these findings suggest that a new class of therapies that selectively inhibit ribosome formation and block protein formation could one day offer effective treatment of human cancers.

Working with pharmaceutical company, Cylene Pharmaceuticals, the researchers have now developed a compound, called CX-5461, that will allow them to test their research in patients. The first-in-human clinical trials to establish the safety profile of this approach will commence in patients with blood cancers at Peter Mac later this year.

“Advanced blood cancers are very difficult to treat and to have a new targeted weapon to test at our disposal is incredibly important and, we hope, another important advance in targeted cancer therapy,” said Dr Simon Harrison, Consultant Haematologist at Peter Mac and Principal Investigator of the upcoming phase 1 trial. “To offer this new trial to Victorians with incurable cancers of the blood system is fantastic and knowing it has the potential to one day help patients across the globe is an incredibly exciting development.”

The team's research appears in the journal Cancer Cell.

Source: Peter MacCallum Cancer Centre

About the Author
Darren Quick Darren's love of technology started in primary school with a Nintendo Game & Watch Donkey Kong (still functioning) and a Commodore VIC 20 computer (not still functioning). In high school he upgraded to a 286 PC, and he's been following Moore's law ever since. This love of technology continued through a number of university courses and crappy jobs until 2008, when his interests found a home at Gizmag.   All articles by Darren Quick
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3 Comments

With 95% of the spending on treatment instead of prevention it is not surprising that the number of cancer related deaths increases year after year. No profit in prevention for the chemical and drug companies which are often one and the same. Nice business model of making money producing and selling toxic chemicals and then make more money creating chemical compounds to treat the people they made deathly ill.

Four times as many Americans die each and every day of the year from the effects of tobacco than died in the trade center on September 11, 2001. The 443,000 death count is equal to the population of some of our red states. The only thing that needs curing to eliminate this cancer is to end corruption in all three branches of government and outlaw the growing and consumption of tobacco.

Calson
10th July, 2012 @ 11:55 am PDT

Calson,

Are you serious? It seems you have inferred that tobacco causes blood cancer? It has nothing to do with it, all genetic I am afraid.

As one of the many unfortunate that suffer from a blood cancer I welcome this development with open arms.

I am a Victorian and get treatment at Peter Mac and I am very proud of their achievements to date with regard to the treatment of cancers. I will be seeing my Oncologist later this week and will put my hand up for this trial.

Saint_cow
10th July, 2012 @ 03:21 pm PDT

Hope you get chosen Saint_cow.

Someday all forms of cancer will be cured.

Calson has a view many agree with...not his anti-tobacco rant, but about pharmaceutical companies eager to provide treatments, instead of cures.

And I'm sure that happens a lot, but some people put what's right, ahead of profits.

Everyone doesn't think the same, it isn't ALL about the money, cures are inevitable.

Derek Howe
10th July, 2012 @ 06:25 pm PDT
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