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Killing cancer without harming healthy cells

A major medical breakthrough in the United Kingdom could lead to the successful treatment of viral cancers, without causing side-effects. 

Researchers funded by Yorkshire Cancer Research and working at York University in northern England used a new technique called RNA interference to destroy human cervical cancer cells grown in culture without causing damage to healthy cells. 

The discovery could have major implications, potentially leading to the successful treatment of cancers caused by viral infection without any harmful side-effects. The research, carried out by Professor Jo Milner and Dr Ming Jiang and published recently in the journal Oncogene, is the first of its kind to use RNA (ribonucleic acid) interference to attack cancerous cells. The impact of the technique – complete elimination of all cancerous cells-was unexpected. 
”Our work has identified a novel agent with major therapeutic potential for the treatment and, possibly, also the prevention of human cervical cancer,” said Professor Milner who leads the team. 

Human cervical cancer, caused by viral infection, is the second most common form of cancer in women worldwide and kills about 1,250 women in the UK alone each year. Cervical cancer develops when the virus attacks the body‘s two front lines of defence, its two tumour suppressors, the proteins p53 and retinoblastoma (Rb). 

In normal cells, Rb controls cell division; p53 has the ability to kill damaged cells that might become cancerous. The virus attacks both these proteins and takes over the reins of cells growth, driving continual out-of-control cell proliferation. 

Dr Jiang and Professor Milner wanted to know if the use of RNA interference - never before used on mammalian cells - could knock out viral genes in the infected cells and restore the body‘s normal defence mechanism. 

The silencing of one viral gene - HPV E6 - caused the growth of the tumour cells to slow and some cells died. Remarkably, when the second viral gene (HPV E7) was silenced, all the cancer cells died. 

Using RNA interference, the infected cells died by a regulated self-destruct process known as apoptosis which enables cells to be removed without inflammatory side-effects. 

It was important to establish that normal healthy cells remained unaffected. In control experiments, researchers found that the anti-viral treatment had no effect on the normal growth and behaviour of non-infected human cells.The successful elimination of cancer cells without adverse effects on normal cells was described by Professor Milner as “absolutely remarkable”. 
”These cancer cells were not engineered in the laboratory,” she said. “They were derived from a human tumour many years ago. Despite growing as cancer cells for years (caused by the viral infection) our work demonstrates that the cells‘ normal control systems have remained intact. As soon as we silenced the viral genes, the infected cancer cells ‘committed suicide‘.” 
Elaine King, chief executive of Yorkshire Cancer Research (YCR) the charity which funded the research said: “This really is encouraging news and proves once again that the research we fund in Yorkshire really is world class. The hard work and dedication of YCR-funded scientists is unwavering and it is this on-going research process that brings about these breakthroughs. 
”While such breakthroughs, by their nature, don‘t happen every day, it is crucial that we continue to fund research for which we continue to rely on the generosity of the people of Yorkshire. I would like to offer my sincere congratulations to Professor Milner, Dr Jiang and their team at York and my thanks to our supporters who have made it all possible.” 

Professor Milner and Dr Jiang are now working on other types of tumours to see if the technique is as effective. Meanwhile, researchers in the United States have found that RNA interference is showing promising results in protecting cells from infection with the HIV virus, signalling that many types of human viral infection could be cured in the future by drugs based on the technique. 

The YCR p53 Research Group in the Department of Biology at York focuses its work on the tumour suppressor p53 present in all tissues of the human body. When p53 is damaged it can no longer protect and this loss of function is linked with the development of more than half of all human cancers. Trying to restore the normal function of p53 is the central tenet of the YCR p53 research group‘s work. 

Yorkshire Cancer Research was founded in 1925 and is the largest independent, regional medical research charity in England and the fourth largest cancer research charity in the UK. It raises about four million pounds sterling annually in Yorkshire and which is used to fund internationally renowned research at five universities in Yorkshire - Bradford, Hull, Leeds, Sheffield and York - and their associated teaching hospitals.

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