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Genome studies give researchers 'panoramic view' of lung cancer

17 September 2012

By John Brinsley

Appeared in BioNews 673

A trio of genetic studies published this week greatly expands researchers understanding of lung cancer.

The studies, published in the journals Cell and Nature, identify new mutations underlying common forms of lung cancer, as well as revealing marked differences in the cancers of patients with and without a history of smoking. It is hoped that the research will provide information for better targeted therapies aimed at treating patients' specific tumour types.

Worldwide, an estimated 1.6 million people are diagnosed with lung cancer each year. The disease has a relatively low five-year survival rate of between 16 and 20 percent and remains one of the world's leading causes of death. While smoking is the primary risk factor, a large proportion of patients who contract the disease have no history of tobacco use.

Professor Ramaswamy Govindan, of Washington University School of Medicine in St Louis, USA, who worked on two of the studies, said that the research gives scientists 'a penthouse panoramic view' of lung cancer, whereas before they had been only 'looking through a keyhole'.

The papers - the first in an expected wave of 'cataloguing studies' - reveal a complex series of genetic changes across the genome, and identify lung cancer as a highly diverse or 'heterogenous' disease. New mutations discovered include those that allow tumours unrestricted growth, or that enable them to evade the body's immune responses. Other mutations have been unearthed in genes involved in DNA repair mechanisms.

As well as revealing new categories of mutations the studies pinpoint marked genetic differences between the tumours of smoking and non-smoking patients. Professor Govindan describes the genomes of smokers as being 'battle-scarred by carcinogen exposure', with mutation rates up to ten times higher than observed in non-smokers, contributing to a much-increased number of mutations.

The studies may inspire better-targeted therapies for lung cancer, as well as refining the approach to clinical trials. Focusing on more specific tumour types means that clinical studies can be smaller, with a greater proportion of participants expected to benefit from treatment. 'When you look for more effective therapies, you don't need larger trials', Professor Govindan explains.

Encouragingly, a number of the mutations identified can be targeted with drugs that are either already licensed or are currently in development for other diseases. Non-smokers in particular were found to be more likely to exhibit mutations in genes such as EGFR and ALK, which can already be targeted by available drugs.

'We found that almost 75 percent of the patients' cancers have mutations that can be targeted with existing drugs - drugs that are available commercially or for clinical trials', Professor Govindan confirms.

However, such news comes with a caveat. Tumours can rapidly become resistant to targeted therapies, with repeat genomic analysis being required in order to select the most appropriate substitutes.

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