(Source: Pharma Times 2014-10-09）
Lung cancers can lie dormant for over 20 years before turning into an aggressive form of the disease.
That is the conclusion from two studies published in Science, one of which was jointly funded by Cancer Research UK and the Rosetrees Trust. In that trial, led by Charles Swanton from CRUKs London Research Institute, researchers studied lung cancers from seven patients – including smokers, ex-smokers and never smokers. They found that after the first genetic mistakes that cause the cancer, it can exist undetected for many years until new, additional, faults trigger rapid growth of the disease.
During this expansion, CRUK notes, there is “a surge different genetic faults appearing in separate areas of the tumour” and “each distinct section evolves down different paths – meaning that every part of the tumour is genetically unique”.
The study also noted that while many of the early genetic faults are caused by smoking, as the disease evolved these became less important. The majority of faults were now caused by a new process generating mutations within the tumour controlled by a protein called APOBEC.
The researchers argue that the wide variety of faults found within lung cancers “explains why targeted treatments have had limited success”. Attacking a particular genetic mistake identified by a biopsy in lung cancer “will only be effective against those parts of the tumour with that fault, leaving other areas to thrive and take over”.
Opening lung cancer’s evolutionary rule book
Prof Swanton said survival from lung cancer “remains devastatingly low with many new targeted treatments making a limited impact on the disease. By understanding how it develops, we’ve opened up the disease’s evolutionary rule book in the hope that we can start to predict its next steps”.
Nic Jones, CRUK’s chief scientist, said: “This fascinating research highlights the need to find better ways to detect lung cancer earlier when it’s still following just one evolutionary path. If we can nip the disease in the bud and treat it before it has started travelling down different evolutionary routes we could make a real difference in helping more people survive”.
The second study, led by Andrew Futreal at the University of Texas MD Anderson Cancer Center, produced similar findings. Across 11 tumour samples, researchers found only 76% of a tumour’s mutations were ubiquitous, compared to the 70% Prof Swanton’s team found, and “they also spotted the APOBEC signature at work in the lung cancer genome”, CRUK noted.
Commenting on the results, Noel Snell, director of research at the British Lung Foundation, said that late presentation and diagnosis “are key reasons for the very poor survival rates from this disease, which are worse in the UK than in Europe and the USA”. He added that “this exciting new research suggests that if they could be diagnosed at a very early stage in their evolution we might be able to tackle the disease earlier and dramatically improve survival rates”.
He concluded by saying “greater investment in this sort of research is absolutely vital if we are to make significant advances in the management of this terrible condition”.
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