Surgery, Gastroenterology and Oncology

Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer, after hepatocellular carcinoma, and accounts for 10-25% of primary liver cancers (1, 2). CCAs are classified as intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA), according to their anatomical location (3).
CCA is more frequent in South Asia compared to Western countries, because of the increased prevalence of established risk factors, including fluke infections (2). In the USA, the incidence of CCA has increased over the past three decades (4). Surgical resection and transplantation are the only curative treatments for patients with CCA, however the majority of cases are not surgical candidates when diagnosed (5). Even after potentially curative surgery, the prognosis of patients with CCA remains poor with 5 year-survival rates of 20% (6).
Gemcitabine in combination with cisplatin is widely accepted as a frontline standard therapy for advanced or metastatic CCA (7).
However, beyond these treatments, there are limited effective systemic therapy options. Recently, an array of actionable genetic alterations has been identified in CCA (8).
Studies evaluating these biomarkers could provide insights into the mechanisms of CCA tumorigenesis and identify potential targets for therapy (9).
Genome-wide characterization have highlighted differing molecular aberrations of CCA and they could help to stratify CCA patients for molecularly targeted therapies (10). Previous studies have investigated roles of genetic, epigenetic and transcriptomic alterations along with well characterized paradigms such as oncogene and tumor-suppressor alterations.

Additionally, the comparison between CCA and benign disease has been useful in identifying differences in carcinogenic mechanisms (11). These studies identified genetic alterations in CCA that could potentially lead to early diagnosis and precision treatment.
This review article discusses the potential therapeutic biomarkers in CCA and the steps for their clinical translation.

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