Lung cancer is the leading type of malignant tumour among
cancer-caused death worldwide, and the 5-year survival rate of
lung cancer patients is only 18%. Various oncogenes are abnormally overexpressed in
lung cancer, including
cancer/testis antigens (CTAs), which are restrictively expressed in the male testis but are hardly expressed in other normal tissues, if at all. CTAs are aberrantly overexpressed in various types of
cancer, with more than 60 CTAs abnormally overexpressed in
lung cancer. Overexpression of oncogenic CTAs drives the initiation,
metastasis and progression of
lung cancer, and is closely associated with poor prognosis in
cancer patients. Several CTAs, such as XAGE, SPAG9 and AKAP4, have been considered as
biomarkers for the diagnosis and prognostic prediction of
lung cancer. More interestingly, due to the high immunogenicity and specificity of CTAs in
cancer, several CTAs, including CT45, BCAP31 and ACTL8, have been targeted for developing novel
therapeutics against
cancer. CTA-based
vaccines,
chimeric antigen receptor-modified T cells (CAR-T) and small molecules have been used in
lung cancer treatment in pre-clinical and early clinical trials, with encouraging results being obtained. However, there are still many hurdles to be overcome before these
therapeutics can be routinely used in clinical
lung cancer therapy. This review summarises the recent rapid progress in oncogenic CTAs, focusing on CTAs as
biomarkers for
lung cancer diagnosis and prognostic prediction, and as targets for novel anti-
cancer drug discovery and
lung cancer therapy. We also identify challenges and opportunities in CTA-based
cancer diagnosis and treatment. Finally, we provide perspectives on the mechanisms of oncogenic CTAs in
lung cancer development, and we also suggest CTAs as a new platform for
lung cancer diagnosis, prognostic prediction, and novel anti-
cancer drug discovery.