Lung cancer – the leading cause of cancer death in the US – can lie hidden within the body for over 20 years before suddenly becoming a rapidly growing and aggressive disease, researchers have discovered.
A recent study, conducted by scientists at Cancer Research UK and published in the journal Science, reveals that after the initial genetic fault that causes cancer in the patient, the disease can remain dormant and undetected for a long period of time, only to become aggressively active when triggered by additional, new genetic mistakes.
The cancer expands when further genetic faults occur in different areas of the tumor. These faults evolve down different paths, leading to a tumor consisting of multiple genetically unique parts.
This discovery explains why targeted treatments are often of limited success. A lung cancer biopsy may identify a specific genetic fault for treatment to target, but in attacking parts of the tumor sharing that particular fault, the areas that share a different genetic mistake are untouched and free to take over.
“Survival from lung cancer remains devastatingly low with many new targeted treatments making a limited impact on the disease,” says study author Dr. Charles Swanton. “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.”
According to the Centers for Disease Control and Prevention (CDC), 207,339 people in the US were diagnosed with lung cancer in 2011. A total of 156,953 people died during the same year. Two-thirds of patients are diagnosed with advanced forms of the disease when treatments are less likely to be successful – a stark statistic that underscores the pressing need for better ways to detect the disease earlier.
Smoking linked to initial genetic faults
For the study, the team analyzed lung cancer tissues from seven patients. This group comprised of a mixture of smokers, former smokers and people who had never smoked before.
The study also assessed how smoking impacted on the development of lung cancer, and the researchers found that many of the initial genetic faults leading to lung cancer were caused by smoking. However, as the cancer grew, these mistakes became less important, with a new process controlled by a protein called APOBEC responsible for creating multiple new mutations.
By revealing that lung cancers can lie dormant for many years the researchers hope this study will help improve early detection of the disease. According to Cancer Research UK, less than 10% of lung cancer patients survive for 5 years or more following diagnosis.
“This fascinating research highlights the need to find better ways to detect lung cancer earlier when it’s still following just one evolutionary path,” says Cancer Research UK lead scientist Dr. Nic Jones. “If we can nip the disease in the bud and treat it before it has started traveling down different evolutionary routes, we could make a real difference in helping more people survive the disease.”
The organization will attempt to take these findings further by funding a study called TRACERx. This study will analyze the lung cancers of hundreds of patients, observing how they evolve over time. In doing so, they hope to discover precisely how lung cancers adapt, mutate and develop resistance to treatments.
“Late presentation and diagnosis are key reasons for the very poor survival rates from this disease, which are worse in the UK than in Europe and the US,” said Dr. Noel Snell. “Greater investment in this sort of research is absolutely vital if we are to make significant advances in the management of this terrible condition.”