Molecular Profile of Intrahepatic Cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease’s underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC’s molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

Editorial: Liver cancer awareness month 2023: current progress and future prospects on advances in primary liver cancer investigation and treatment

“…Continuous liver damage and regeneration lead to cellular mutations and malignant transformation. Recent molecular investigations have identified several key pathways involved in cancer development for hepatocellular carcinoma and cholangiocarcinoma, including the Wnt/β-catenin, PI3K/AKT, and MAPK signaling pathways, which play critical roles in cell proliferation, survival, and apoptosis ( 3 , 4 ). Other factors, such as excessive alcohol consumption and exposure to toxins, also play critical roles in liver carcinogenesis by direct DNA damage.…”

The role of living donor liver transplantation in treating intrahepatic cholangiocarcinoma

“…The prognosis is usually dismal, with a reported 5-year overall survival of 10% to 35%. However, the prognosis is strictly related to stage and molecular profiles ( 5 ). The recommended treatment for advanced stages is chemotherapy combined with immunotherapy, with a median overall survival of less than one year ( 6 , 7 ).…”