Blood-based biomarkers for lung cancer: Ready for prime time?

Abstract

Blood based biomarkers have the potential for improving outcomes in lung cancer, a disease where approximately 40% of patients present with distant metastases at diagnosis. Two important areas of research include the discovery of risk biomarkers (e.g. defining who will develop lung cancer in the future) and the identification of diagnostic biomarkers for use as a screening tool or to assess the likelihood of cancer in patients with a radiographic abnormality such as a lung nodule. Although the pace of biomarker discovery is advancing rapidly across all of these areas, the development of biomarkers to assess the likelihood of cancer in patients with lung nodules has been an intense area of research and several biomarkers are currently being evaluated in prospective trials. Lung nodules are increasingly identified either incidentally or through the use of screening low dose chest CT. Lung nodules deemed indeterminate lack the features suggestive of benign etiologies and present clinicians with a diagnostic conundrum. Although most lung nodules are benign, patients frequently undergo multiple diagnostic tests, including the use of positron emission tomography (PET), as well as invasive procedures such as transthoracic needle aspiration, bronchoscopy and/or surgery. Therefore, biomarker strategies to distinguish between malignant and benign lung nodules may mitigate the diagnostic burden faced in this setting. Peripheral blood based detection strategies are an attractive approach for diagnostic markers, given the ease of acquisition and potential for serial testing, and are based on the underlying hypothesis that molecular alterations of tumor cells lead to the synthesis of distinct molecular species that can be detected in the blood. Peripheral blood biomarkers have been identified in both the cellular component (circulating tumor cells, white blood cells) and in the non-cellular fraction (e.g. plasma, serum), and studies have spanned across several different types of molecular species. The presentation will review the rationale for the use of early detection biomarkers for risk assessment, screening, and diagnosis, and provide a comprehensive overview of blood based biomarkers currently in development, including markers that are available for clinical use. This will include an analysis of existing data from clinical validation and utility studies supporting the use of blood based diagnostic tests as well as a discussion of ongoing prospective trials.