Abstract
Simple SummaryBile 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.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.
Highlights
Cholangiocarcinomas (CCA) are a group of cancers of the biliary system which are usually diagnosed late, often with a dismal prognosis [1,2,3,4]
In cases where no annotated protein level data was reported in the Human Protein Atlas, biomarkers were included in the data extraction unless the study reported upregulation in normal tissues which fulfilled the exclusion criteria
We describe a method for systematic review of literature for the identification of theranostic biomarkers and assessment of biomarker characteristics according to their theranostic potential which involves the utilization of freely available bioinformatics tools to gather validated information
Summary
Cholangiocarcinomas (CCA) are a group of cancers of the biliary system which are usually diagnosed late, often with a dismal prognosis [1,2,3,4]. There is geographical variation in the incidence of CCA with higher incidence in Eastern countries compared to Western nations where this is a rare, sporadic cancer [5,6]. This cancer is especially prevalent in Thailand, where CCA is a significant national health burden due to the prevalence of the liver fluke, which is an etiological factor [7]. The median overall survival even with palliative chemotherapy remains less than twelve months [9] To improve these poor outcomes, discovery of new diagnostic markers, development of targeted therapies to improve the translation of new strategies such as nanomedicine-based technology, and predictive markers to determine response to therapy should be explored. There has been a recent push towards the identification of genetic drivers of CCA progression and this may reveal specific markers which could expedite the development of more effective and individualized therapies [10,11]
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