Translating Biomarkers of Cholangiocarcinoma for Theranosis: A Systematic Review

SIMPLE SUMMARY: Bile duct cancers are rare cancers that have poor prospects and limited treatment options. Recently, significant advances have been made in the field of nanomedicine which has allowed new approaches to the diagnosis and treatment (i.e., theranosis) of human diseases. To develop nanomedicines that could earmark or target bile duct cancer, specific proteins (or biomarkers) that are present in bile duct cancer but absent in normal tissues are required. We conducted a systematic search of the published literature for bile duct cancer biomarkers that would be suitable for theranosis. Specialist bioinformatics tools were used to help categorize the resulting data set. To select the most promising biomarkers from the search, biomarkers were ranked according to a theranosis-scoring-system and then evaluated in detail. The biomarkers identified using this approach have the potential to promote targeted nanomedicine-based systems to treat bile duct cancers. ABSTRACT: Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996–2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis.