The state of molecular biomarkers for the early detection of lung cancer

Abstract

Using biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent has been the goal of many investigations. Recent advances in molecular strategies and analytic platforms, including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers in the blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum, but none have yet moved to the clinical setting. Therefore, there is a recognized gap between the promise and the product delivery in the cancer biomarker field. In this review, we define clinical contexts where risk and diagnostic biomarkers may have use in the management of lung cancer, identify the most relevant candidate biomarkers of early detection, provide their state of development, and finally discuss critical aspects of study design in molecular biomarkers for early detection of lung cancer.

Figure 1

Clinical contexts for biomarker development in early detection of lung cancer. This diagram illustrates 4 clinical contexts within 4 windows of time. The period during which lung cancer is nonmeasurable and precedes the diagnosis characterizes the context of risk assessment. It represents a long window of time during which the disease develops and corresponds to an opportunity for chemoprevention. When the disease becomes measurable but remains asymptomatic, we enter the context of early diagnosis. Two other clinical contexts relate to clinical diagnosis, that is, when the disease is measurable and patients symptomatic, and to detection of recurrence. These windows of time correspond to the different contexts for which different biomarker targets can be developed. Adapted from Hassanein and colleagues (109). Adapted with permission of the American Thoracic Society. Copyright © 2012 American Thoracic Society.