Lung cancer biomarkers, targeted therapies and clinical assays

Abstract

Until recently, the majority of genomic cancer research has been in discovery and validation; however, as our knowledge of tumor molecular profiling improves, the idea of genomic application in the clinic becomes increasingly tangible, paralleled with the drug development of newer targeted therapies. A number of profiling methodologies exist to identify biomarkers found within the patient (germ-line DNA) and tumor (somatic DNA). Subsequently, commercially available clinical assays to test for both germ-line and somatic alterations that are prognostic and/or predictive of disease outcome, toxicity or treatment response have significantly increased. This review aims to summarize clinically relevant cancer biomarkers that serve as targets for therapy and their potential relationship to lung cancer. In order to realize the full potential of genomic cancer medicine, it is imperative that clinicians understand these intricate molecular pathways, the therapeutic implication of mutations within these pathways, and the availability of clinical assays to identify such biomarkers.

Keywords: Assay; biomarker; lung cancer; mutation; pharmacogenetic.

Figure 1

Example of a biomarker-driven treatment pathway for NSCLC, whereby mutations in EGFR or ALK drive targeted therapy selection, while patients with tumors negative for these biomarkers have therapy guided by histology and other clinical factors. NSCLC, non-small cell lung cancer; ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; ROS1, ROS proto-oncogene 1, receptor tyrosine kinase.