Improvements in outcomes for cervix cancer and bowel cancer provide support for the concept that early diagnosis has the greatest promise to improve cancer outcomes. Unfortunately, our improved understanding of the molecular basis of lung cancer has not translated into effective means for early detection. There is at the present time a substantial need for simple but accurate non-invasive tests to detect lung cancer before it is advanced to the point that treatment is rendered ineffective. Blood-based biomarker tests provide an ideal approach given that asymptomatic subjects have blood drawn at the time of routine check-ups. However, while the concept of blood-based cancer tests is simple, the development of such tests has been quite challenging to the point that very few such tests have reached the Food and Drug Administration (FDA) in recent years. Worse yet, numerous claims have been made based on limited data and faulty experimental design. This situation may be attributed historically to (1) limited availability of in-depth discovery technologies and limited understanding of tumor heterogeneity to guide the development of biomarkers; (2) insufficient resources and incentives to develop and maintain collaborative teams able to impact the problem; (3) ad-hoc single investigator-based efforts with limited resources to accomplish objectives; and (4) limited availability of appropriate quality specimens for discovery and validation studies that overcome the biases inherent in sample collections. It is now time for a paradigm shift in the way we approach the development of blood based cancer tests to overcome past limitations. To this effect and following the RFA concept, we have assembled a multidisciplinary team with expertise and track record in genomic, proteomic, and metabolomic analysis of blood able to meet the challenges of developing blood tests based on panels of markers that detect the presence of lung cancer at the pre-symptomatic stage. The public health impact of the development of effective blood-based tests for the detection of lung cancer are quite substantial given the millions of subjects who are at risk for lung cancer due to current smoking or a past history of smoking and the current available modality for screening consisting of expensive, unreliable scans. Additionally, if proven effective, blood tests may be applicable to non-smoker subjects given that never smokers with lung cancer represent some 15% of cases and lung cancer among never smokers is number 7 on the top 10 list of cancer killers.

Initially, we conceive of the blood tests as being utilized to assist in the interpretation of CT (computer tomography) scans. Given the limited reliability of such scans, with problems associated with difficulty in distinguishing benign from malignant lesions and the emerging problem of overdiagnosis, a blood-based test would improve the reliability of imaging modalities to detect and diagnose lung cancer. A reliable blood test would reduce unnecessary surgery if we can distinguish between lesions on a CT that are due to cancer from lesions that not due to cancer and therefore would not require surgery. However, if the blood test turns out to be quite promising, it may eventually be the frontline test for screening for lung cancer with CT scans used on a more limited basis when the blood test comes out positive.

We are projecting that within a timeframe of 3 years of funding for this project, we would have enough time to determine which of the candidate biomarkers we have available pass initial pre-validation criteria to be included in a panel that would then undergo validation to demonstrate success in detecting lung cancer before onset of symptoms and in distinguishing malignant from benign lesions observed on CT scans. If we do achieve such success as we hope, then adoption and deployment of such blood test would likely follow rapidly.