Cancer-testis antigens (CTAs) in lung cancer

The predominant cause of cancer-related death worldwide is lung cancer. Poor survival rates are mainly due to late diagnosis due to the lack of sensitive and specific biomarkers and analytical tools. In this review, we examine the use of cancer-testis antigens (CTAs) as potential biomarkers due to their increased expression in malignancy. For example, the diagnostic potential of New York esophageal squamous cell carcinoma 1 (NY-ESO-1) autoantibodies was low for sensitivity (48.3%) but higher for specificity (90.9%) in small cell lung cancer (SCLC). In contrast, A-kinase anchoring protein 4 (AKAP4) peripheral blood mononuclear cell (PBMC) quantitative polymerase chain reaction (qPCR) was 92.8% (sensitivity) and 92.6%, (specificity) in non-small cell lung cancer (NSCLC). We assess existing knowledge regarding CTAs and compare their effectiveness vs other markers such as NY-ESO-1, melanoma-associated antigen A (MAGE-A), sperm-associated antigen 9 (SPAG9), AKAP4, X antigen family member 1 (XAGE-1) and B-cell receptor-associated protein 31 (BCAP31). We also discuss the incorporation of CTA testing in lung cancer diagnostic workflows with focus on its analytical performance, preanalytical factors as well as comparative value vs existing markers. Finally, we outline the role of CTAs as companion diagnostics in immunotherapy and targeted treatment plans, and indicate the main challenges and research priorities towards the clinical translation of CTAs.