Protein-based biomarkers in pulmonary malignancies

Targeted therapies have revolutionised the management of patients with lung cancer over the last 20 years. A crucial role for pulmonary pathologists is to provide high quality and timely analysis of predictive biomarkers that guide the use of these targeted treatments. Protein-based biomarkers, alongside nucleic acid analyses, are mostly used to predict response to therapies that inhibit oncogenic stimulation or utilise immune checkpoint inhibition. Despite the protein-based mechanism of action of targeted therapies, development of biomarkers for lung cancers have been chiefly focused on genomics. With ongoing expansion of targeted treatments, including novel classes of therapeutics such as antibody drug conjugates, and an increasing requirement for effective biomarkers, however, immunochemistry and related techniques may still continue to play a valuable and crucial role in predictive profiling. This review will focus on current and future protein-based biomarkers in pulmonary malignancies alongside the assays, underlying biology and appropriate clinical context required to effectively utilise them. This will provide an overview of the role of the pathologist in effectively guiding targeted treatments for lung cancer patients.