Lung cancer can stay dormant for 20 years until triggered by genetic
13 October 2014
Researchers at Cancer Research UK have discovered that lung
cancers can lie dormant for over 20 years until genetic faults
trigger sections to grow and the cancer becomes aggressive.
The team 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.
Tumour has genetically distinct parts
During this expansion there is a surge of different genetic
faults appearing in separate areas of the tumour. Each distinct
section evolves down different paths — meaning that every part of
the tumour is genetically unique.
This research — jointly funded by Cancer Research UK and the
Rosetrees Trust and published in the journal Science —
highlights the need for better ways to detect the disease earlier.
Two-thirds of patients are diagnosed with advanced forms of the
disease when treatments are less likely to be successful.
By revealing that lung cancers can lie dormant for many years the
researchers hope this study will help improve early detection of the
Treatment needs to target each genetically distinct area
Study author Professor Charles Swanton, at Cancer Research UK’s
London Research Institute and the UCL Cancer Institute, 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
The study also highlighted the role of smoking in the development
of lung cancer. Many of the early genetic faults are caused by
smoking. But as the disease evolved these became less important with
the majority of faults now caused by a new process generating
mutations within the tumour controlled by a protein called APOBEC.
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.
Over 40,000 people are diagnosed with lung cancer each year and,
despite some positive steps being made against the disease it
remains one of the biggest challenges in cancer research, with fewer
than 10 per cent surviving for at least five years after diagnosis.
Building on this research will be a key priority for the recently
established Cancer Research UK Lung Cancer Centre of Excellence at
Manchester and UCL. The Centre, where Professor Swanton is joint
centre lead, is a key part of Cancer Research UK’s renewed focus to
beat lung cancer; bringing together a unique range of
internationally renowned scientists and clinicians to create an
environment that catalyses imaginative and innovative lung cancer
Professor Nic Jones, Cancer Research UK’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
“Building on this work Cancer Research UK is funding a study
called TRACERx which is studying 100s of patient’s lung cancers as
they evolve over time to find out exactly how lung cancers mutate,
adapt and become resistant to treatments.”
de Bruin, EC et al. Spatial and temporal diversity in genomic
instability processes defines lung cancer evolution. Science (2014)