Intrahepatic Cholangiocarcinoma: A Summative Review of Biomarkers and Targeted Therapies

SIMPLE SUMMARY: Intrahepatic cholangiocarcinoma is the second most common primary liver malignancy. Among patients with operable disease, surgical resection is the cornerstone of therapy. Among the majority of patients who present with advanced disease treatment, systemic or targeted therapy is indicated. Recent advancements have provided more novel therapeutic approaches to a subset of patients with intrahepatic cholangiocarcinoma. ABSTRACT: Although rare, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy and the incidence of ICC has increased 14% per year in recent decades. Treatment of ICC remains difficult as most people present with advanced disease not amenable to curative-intent surgical resection. Even among patients with operable disease, margin-negative surgical resection can be difficult to achieve and the incidence of recurrence remains high. As such, there has been considerable interest in systemic chemotherapy and targeted therapy for ICC. Over the last decade, the understanding of the molecular and genetic foundations of ICC has reshaped treatment approaches and strategies. Next-generation sequencing has revealed that most ICC tumors have at least one targetable mutation. These advancements have led to multiple clinical trials to examine the safety and efficacy of novel therapeutics that target tumor-specific molecular and genetic aberrations. While these advancements have demonstrated survival benefit in early phase clinical trials, continued investigation in randomized larger-scale trials is needed to further define the potential clinical impact of such therapy.