Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive and heterogeneous biliary cancer with a poor prognosis and limited treatment options. The molecular pathogenesis of iCCA involves a highly complex process entailing multiple genetic alterations and dysregulation of signaling pathways. Recent advancements in our understanding of the genetic landscape of iCCA have opened new opportunities for therapeutic interventions. Technologies such as next-generation sequencing (NGS) have contributed to elucidating the genetic heterogeneity of iCCA, leading to the identification of numerous potentially actionable genetic alterations. Despite these advances, the prognosis of iCCA patients remains dismal. In this review, we provide an extensive summary of the current knowledge on genetic alterations in iCCA, their biological impact on patients, potential therapeutic targets, approved targeted therapies, and ongoing clinical trials with targeted agents. Furthermore, we discuss the main technologies available for studying genetic alterations and their advantages and limitations. Finally, we highlight future directions in studying genetic alterations and the development of new targeted therapies and personalized medicine approaches.
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