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
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
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.