Next-Generation Biomarkers for Cholangiocarcinoma

SIMPLE SUMMARY: Early and non-invasive diagnosis of cholangiocarcinoma (CCA) is still challenging, thus largely contributing to the increased mortality rates observed worldwide. Consequently, several efforts have been made in order to report novel biomarkers for CCA, that would aid on diagnosis and also to predict prognosis and therapy response. We herein aim to provide an in-depth and critical revision on the next-generation biomarkers for CCA that have been recently proposed. ABSTRACT: The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.