Scientists have discovered that lung cancers can lie dormant for
over 20 years before suddenly turning into an aggressive form of
the disease.
The team at Cancer Research UK's London Research Institute
(LRI; now part of the Francis Crick Institute) 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 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 highlights the need for better ways to detect the
disease earlier. Two-thirds of patients are diagnosed with advanced
forms of lung cancer 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 disease.
Professor Charles Swantonof LRI said: "Survival from lung cancer
remains devastatingly low with many new targeted treatments making
a limited impct 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."
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.
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 disease."
The paper, Spatial and
temporal diversity in genomic instability processes defines lung
cancer evolution, is published in Science.