Experimental drug activates key anti-cancer mechanism
An experimental drug can reactivate a key cancer-fighting mechanism inside cancer cells, according to Australian researchers.
The drug, called CX-5461, initiates a cascade of events that ultimately switches on the p53 'tumour suppressor' protein.
Discovered in the 1970s by Cancer Research UK researchers, p53 is found in all human cells, and is a central part of the body's anti-cancer defences. But it is faulty or inactivated in the majority of cancers.
The experimental drug was shown to selectively kill off lymphoma and leukaemia cells in mice, and clinical trials in cancer patients are now planned.
The drug is manufactured by Cylene Pharmaceuticals.
Commenting on the research, Dr Carlos Rubbi, of the Liverpool Cancer Research UK Centre, said scientists have been trying for years to find ways to switch on p53 in tumours to stop them growing.
"This is early lab research, but this team seem to have found a potential strategy to do just that, so this is very significant work," he added.
"It builds on fundamental research by Cancer Research UK scientists and others into how tiny 'factories' inside the centre of cells - called nucleoli - are involved in regulating p53, the most important cancer-protective molecule in the body."
Nucleoli are found inside a cell's nucleus, and are where certain genes are 'read' to form the components of ribosomes, the tiny cellular machines that make proteins.
For more than a century scientists knew that cancer cells contain abnormal nucleoli, but did not know whether this was a cause of cancer, or a product of it.
In the new research, a team led by Dr Ross Hannan of the Peter MacCallum Cancer Centre in Melbourne has provided evidence showing that accelerated reading of ribosomal genes is responsible for causing abnormal nucleoli and is necessary for the survival of cancer cells.
Dr Hannon said: "The work in this study demonstrates that cancer cells are far more dependent on their ability to make ribosomes than normal cells.
"Critically, we demonstrate that selective inhibition of the enzyme RNA polymerase I, that is responsible for synthesising the major ribosomal components, can be used to selectively kill cancer cells while leaving normal cells untouched."
The findings also show that blocking this accelerated reading in mice can set off a cascade of events that causes lymphoma and leukaemia cells to die, while sparing normal cells.
But Dr Rubbi cautioned that the research was still at an early stage: "This is an elegant study, and it will be interesting to see if this early promise is translated into results in the clinic."
The work is published in the journal Cancer Cell.
Copyright Press Association 2012