The loss of a single type of protein molecule may play a key role in the development of 75% of the most common kind of lung cancer, research suggests.
Lung cancer kills 30,000 in the UK each year
The researchers, from Vanderbilt University in Nashville, hope the finding could lead to new treatments for non-small cell lung cancer.
The proteins help control cell growth and suicide, and blood vessel formation - all of which can go awry in cancer.
The study is published in the British Journal of Cancer.
Lung cancer accounts for 5% of all deaths and 22% of all cancer deaths in the UK
It is the most common cause of cancer death for both men and women
More cases diagnosed in men, but the numbers of women being diagnosed has increased
Around 20% are small cell lung cancers
The rest are non-small cell lung cancers
Smoking and passive smoking cause 90% of cases
Lung cancer remains the leading cause of cancer death in the world with more than 1.2 million new cases diagnosed every year, including more than 37,000 in the UK.
Despite major advances in the understanding and treatment of the disease, it is still one of the most difficult cancers to treat.
The researchers compared samples of lung tumour tissue and corresponding healthy lung tissue taken from 46 lung cancer patients.
They found that the key proteins were almost completely missing or were much reduced in 77% of the tumour samples.
To confirm the importance of the proteins, the researchers examined tumour cells injected and grown in mice.
They found cancer cells carrying the proteins formed smaller, less aggressive tumours than cells which did not.
Lead researcher Professor Pran Datta said: "We've established for the first time that these important molecules are either missing or that their action is reduced in three quarters of all cases of lung cancer.
"When we restored the molecules in lung cancer cells in mice they reduced the ability of the cells to grow as tumours."
Professor Datta said the next step would be to discover how the proteins were lost during the development of lung cancer.
Finding a way to intervene could lead to the development of new treatments for the disease.
Professor John Toy, of Cancer Research UK, said: "Unravelling events that lead to the loss of normal molecules in cancer is extremely important in finding new ways to control the disease.
"However, it's important to remember that the vast majority of cases of lung cancer are preventable as they are caused by smoking. The best way to reduce risk is to quit."
The key proteins are called type 2 receptors for Transforming Growth Factor-b (TGF-b).
It is members of the TGF-b family that control cell growth and death, and blood vessel formation.