Tumors shed cells into the blood or sputum, signs of which could theoretically be picked up in noninvasive tests. But finding biomarkers that can aid in diagnosis of lung cancer has been challenging. "In the past, we have tried to look in the blood for differences between healthy people and cancer patients," says Carbone. "We've had some success, but it's not as specific as we would like." So researchers are now looking for markers specific to tumor cells, and then determining whether those markers are detectable in blood.

Using mass spectrometry to identify tumor-derived proteins, scientists have so far identified a promising set of candidate biomarkers. In a study of tissue samples from about 100 patients, researchers found that adding the blood test to standard imaging tests could more accurately diagnose lung cancer. In a second study, researchers used a genetic analysis technique called array CGH, which detects small structural variations, such as extra copies of a piece of the genome, to identify a number of variations found specifically in the very early stages of lung cancer.

The researchers then designed a diagnostic test to detect four of the cancer-specific structural variations. In a similar retrospective study of tissue samples, researchers found that the new test improved the odds of correctly diagnosing the disease. The downside to this approach, however, is that it requires a biopsy to get tumor-cell samples, which is more invasive than a simple blood test.

Massion and his collaborators are now studying the genes affected by these variations for clues to their role in lung cancer. They would also like to identify biomarkers that can distinguish dangerous cancers from potentially less troublesome ones. Several studies show that early screening can detect small cancers, which scientists had assumed were precursors to the larger cancers seen in patients in later stages of the disease. However, the results of these studies suggest that "the cancers detected very early on seem to be biologically distinct from those detected later," says Massion. If that is the case, a wait-and-see approach may be more suitable for these smaller cancers than invasive surgery.