Trio of studies outline 'genomic landscape' of non-small cell lung cancer

In collaboration with the Press Association

Researchers have painted the most detailed picture yet of the faulty genes involved in non-small cell lung cancer (NSCLC), one of the world's most hard-to-treat cancers.

The work, published as three papers in the journals Cell and Nature, could ultimately lead to lung cancer patients being given treatments tailored to their tumour's genetic features, the researchers say.

As well as finding genetic faults never previously linked to NSCLC, the scientists found that tumours from smokers had different genetic faults, and much more DNA damage, than tumours from non-smokers.

A researcher involved in two of the studies, Dr Ramaswamy Govindan of Washington University School of Medicine, said further research to fully understand the "genomic landscape" of lung cancer will help identify new targets for therapy.

The studies looked at different forms of NSCLC, the most common type of lung cancer.

NSCLC is an umbrella term for different sub-types of NSCLC called squamous cell carcinoma, adenocarcinoma and large cell carcinoma. These respond to treatment in a different way to the other main type of lung cancer, small cell lung cancer.

Two of the studies, published in Nature and Cell respectively, analysed the genetic code of tumours from 178 patients with lung squamous cell carcinomas, and 183 with lung adenocarcinomas.

In a third, smaller, study, also published in Cell, scientists analysed 17 NCSLC tumours from smokers and from patients who had never smoked. The researchers, led by Dr Govindan and Dr Richard Wilson of Washington University School of Medicine, found that smokers had 10 times as many genetic changes in their tumours than tumours from non-smokers.

In non-smokers, the researchers found at least one mutated gene that can be targeted with drugs currently on the market or available through clinical trials. Across all patients, the team identified 54 genes that could be targeted by existing drugs.

Dr Wilson and Dr Govindan were also involved in the squamous cell carcinoma study, the findings of which mirrored that of their smaller study. They found a wide array of genetic changes in different squamous cell carcinoma tumours, many of which could be targeted with existing drugs.

Dr Wilson predicts that the standard approach to treating cancer will be based on the genes that are found to be altered, rather than the organ in which it originates. For example, instead of calling it 'lung cancer', doctors may call it 'EGFR cancer's, after the faulty gene driving the tumour's growth.

"For example, if genome sequencing revealed that a lung cancer patient has a mutation known to be sensitive to a drug that works in breast tumours with the same genetic alteration, you may want to use that agent in those lung cancer patients, ideally as part of a clinical trial," he says.

"In the coming years, we hope to be treating cancer based more on the altered genetic make-up of the tumour than by the tissue of origin," he added.

The adenocarcinoma study also discovered differences between the alterations in the genes found in tumours from smokers and non-smokers, as well as finding altered genes that had not previously been linked to cancer before.

"This is the largest genomic study of lung adenocarcinoma to date," says study author Alice Berger of the Broad Institute. "Our results are a testament to the power of large-scale next-generation sequencing technology to expand our understanding of tumour biology."

Professor Charles Swanton, a Cancer Research UK expert, said: "Together these studies provide the most detailed picture yet of the landscape of genes involved in non-small cell lung cancer, a disease that can be very tough to treat successfully."

Professor Swanton pointed out that the fact lung cancers from smokers have 10 times the genetic damage of non-smokers, shows the harmful effects of smoking and reinforces that smoking is by far the biggest single preventable cause of cancer.

"The studies also confirm recent work by Cancer Research UK and others which have shown that cancers aren't made up of just one type of identical cell but in fact consist of different sub-clones within one tumour," he said.

"This helps explain how tumours may become resistant to drugs and why we need to find ways to target the 'mission critical' gene faults that are shared by the majority of tumour cells.

"It's also encouraging that the researchers have discovered gene faults that have never before been linked to lung cancer - this gives us new avenues for research into future treatments," he added.

Copyright Press Association 2012

References

  • Govindan, R. et al. (2012). Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers, Cell, 150 (6) 1134. DOI: 10.1016/j.cell.2012.08.024
  • Imielinski, M. et al. (2012). Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing, Cell, 150 (6) 1120. DOI: 10.1016/j.cell.2012.08.029
  • Hammerman, P.S. et al. (2012). Comprehensive genomic characterization of squamous cell lung cancers, Nature, DOI: 10.1038/nature11404