Abstract
The identification of cancer-specific biomolecules is of fundamental importance to the development of diagnostic and/or prognostic markers, which may also serve as therapeutic targets. Some antigenic proteins are only normally present in male gametogenic tissues in the testis and not in normal somatic cells. When these proteins are aberrantly produced in cancer they are referred to as cancer/testis (CT) antigens (CTAs). Some CTA genes have been proven to encode immunogenic proteins that have been used as successful immunotherapy targets for various forms of cancer and have been implicated as drug targets. Here, a targeted in silico analysis of cancer expressed sequence tag (EST) data sets resulted in the identification of a significant number of novel CT genes. The expression profiles of these genes were validated in a range of normal and cancerous cell types. Subsequent meta-analysis of gene expression microarray data sets demonstrates that these genes are clinically relevant as cancer-specific biomarkers, which could pave the way for the discovery of new therapies and/or diagnostic/prognostic monitoring technologies.
Highlights
Achieving effective treatments for cancers is more difficult once the disease has reached the metastatic stage
High stringency human orthologue identification and filtering for mitotic expression resulted in 375 human genes which were potentially testis spermatocyte /meiosisspecific [44]
If a candidate gene was represented in a non-testis/non-central nervous system (CNS) normal tissue expressed sequence tag (EST) library, it was excluded
Summary
Achieving effective treatments for cancers is more difficult once the disease has reached the metastatic stage. This, in combination with the trend towards personalised approaches to cancer medicine means there is an increasing need to identify and develop cancer-specific biomarkers that can be employed in the development of early, pre-metastatic diagnostic and treatment strategies [1,2,3,4,5,6,7]. CTAs can serve as immunologically restricted cancer-specific antigens, making them exceptionally attractive as diagnostic, prognostic and therapeutic biomarkers/targets, the targeting of which should not induce deleterious side effects to non-cancerous somatic tissue. Www.impactjournals.com/oncoscience the activation of a specific cohort of such genes has been correlated with more aggressive lung cancers [30]. Use of an immunohistochemical approach in non-small cell lung cancers revealed a correlation between survival and the presence of known CTAs [31]. NY-ESO-1 is one of the most immunogenic CTAs and has been used as a successful target for adoptive therapy in the treatment of malignant melanoma [32]
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