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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.


04 November 2013 - by Dr Sarah Spain 
Two recent studies have shown how treatments for lung cancer can be tailored to a tumour's genetic make-up, which may ultimately improve existing treatments or even help to identify new ones...
10 December 2012 - by Purvi Shah 
An average person carries roughly 400 potentially damaging mutations in their DNA, say geneticists...
29 October 2012 - by Rivka Marks-Maran 
Thousands of genetic mutations associated with pancreatic cancer have been identified in an international study...
08 October 2012 - by Paola Quattroni 
A computer-based platform which looks to greatly speed up genetic analysis of tumours has been unveiled in the USA. Currently such analysis can take up to eight weeks, the new platform promises to deliver results in just 47 seconds...

24 January 2011 - by Maren Urner 
A team of US scientists has studied the immediate consequences of cigarette smoking in humans and found cigarette smoke potentially affects genes within a timescale of minutes....
21 December 2009 - by Alison Cranage 
Scientists at the Wellcome Trust Sanger Institute have sequenced the genomes of two cancers - malignant melanoma skin cancer and an aggressive form of lung cancer. Their findings were published in Nature last week and could transform cancer treatments....
09 November 2009 - by Ailsa Stevens 
A UK company has launched a genetic test aimed at predicting the risk of smokers developing lung cancer. The test, known as Respirigene, assesses 20 different genetic markers which have previously been linked to lung cancer in combination with other known risk factors for the disease, such as age, any prior medical history of chronic lung disease, and family history of lung cancer, to decide whether an individual is in a high, moderate or low risk category for lung cancer....
05 January 2009 - by Ailsa Stevens 
Individuals with alterations in ABCB1 and ABCC1, two genes thought to be involved in getting rid of inhaled toxins from the lungs, may have an increased risk of developing lung cancer, according to a new study published in the journal Cancer. The research, carried out by Chinese...

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