Lung Cancer Can Lie Hidden For 20 Years

Lung cancer can lie hidden for over 20 years.
Lung cancer can lie dormant for more than 20 years before turning deadly, helping explain why the disease is so persistent and difficult to treat. Two papers in the journal Science reveal how lung cancer evolves.

After an initial disease-causing genetic fault, tumour cells quietly develop numerous new mutations, making different parts of the same tumour genetically unique. By the time patients are sick enough to be diagnosed with cancer, their tumours will have developed down multiple evolutionary pathways, making it extremely hard for any targeted medicine to have an effect. The findings show the pressing need to detect lung cancer before it has shape-shifted into multiple malignant clones, say the researchers of one of the papers.

Lung cancer is the world's deadliest cancer, killing an estimated 4,300 people a day, according to the World Health Organization. Around 85 percent of patients have non-small cell lung cancer (NSCLC), the type analysed in the two studies.

To get a clearer understanding of the disease, the scientists looked at genetic variability in different regions of lung tumours removed during surgery and worked out how genetic faults had developed over time. What they found was an extremely long latency period between early mutations and clinical symptoms, which finally appeared after new, additional faults triggered rapid disease growth.
In the case of some ex-smokers, the initial genetic faults that started their cancer dated back to the time they were smoking cigarettes two decades earlier. But these faults became less important over time and more recent mutations were caused by a new process controlled by a protein called APOBEC.

Apart from better drugs, a critical challenge is to find improved ways to detect lung cancer before it develops the multiple genetic faults that eventually trigger rapid tumour growth and spread.
Currently, doctors use computerised tomography (CT) to detect lung cancer -- but by the time a nodule is big enough to be spotted it on a scan it may contain a billion genetically diverse cancer cells.
 
The researchers of the second paper suggest that it may be possible to detect mutations in lung cancer cells using a single biopsy. They analysed a type of non-small cell cancer called an adenocarcinoma, cancer that forms in the epithelial cells that line the lung. They identified over 7000 mutations and found on average 76 per cent of all mutations and 20 out of 21 known cancer gene mutations were found in all regions of the same tumour.
 
The current prognosis for NSCLC is grim, with most patients diagnosed when the disease has already spread and only around 15 per cent surviving for at least five years after that.
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