Cancer-testis antigens: Unique cancer stem cell biomarkers and targets for cancer therapy

Cancer-testis antigens (CTAs) are considered as unique and promising cancer biomarkers and targets for cancer therapy. CTAs are multifunctional protein group with specific expression patterns in normal embryonic and adult cells and various types of cancer cells. CTAs are involved in regulating of the basic cellular processes during development, stem cell differentiation and carcinogenesis though the biological roles and cell functions of CTA families remain largely unclear. Analysis of CTA expression patterns in embryonic germ and somatic cells, pluripotent and multipotent stem cells, cancer stem cells and their cell descendants indicates that rearrangements of characteristic CTA profiles (aberrant expression) could be associated with cancer transformation and failure of the developmental program of cell lineage specification and germ line restriction. Therefore, aberrant CTA profiles can be used as panels of biomarkers for diagnoses and the selection of cancer treatment strategies. Moreover, immunogenic CTAs are prospective targets for cancer immunotherapy. Clinical trials testing broad range of cancer therapeutic vaccines against antigens of MAGEA and NY-ESO-1 families for treating various cancers have shown mixed clinical efficiency, safety and tolerability, suggesting the requirement of in-depth research of CTA expression in normal and cancer stem cells and extensive clinical trials for improving cancer immunotherapy technologies. This review focuses on recent advancement in study of CTAs in normal and cancer cells, particularly in normal and cancer stem cells, and provides a new insight into CTA expression patterns during normal and cancer stem cell lineage development. Additionally, new approaches in development of effective CTA-based therapies exclusively targeting cancer stem cells will be discussed.