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Page 2 of 13 Pan et al. Hepatoma Res 2024;10:3 https://dx.doi.org/10.20517/2394-5079.2023.44

the bile ducts. It is a rare and aggressive disease that can develop in various locations along the biliary tract.

In clinical practice, magnetic resonance imaging (MRI) plain scans and dynamic contrast-enhanced scans
are commonly employed for the diagnosis of hepatocellular carcinoma (HCC) and cholangiocarcinoma.
Specifically, during the arterial phase, hepatocellular carcinoma typically exhibits uniform hypervascularity,
accompanied by a significant reduction in enhancement during the portal vein phase, which is lower than
[1]
that of the normal liver parenchyma . In contrast, ICC manifests as heterogeneous hypervascularity in the
arterial phase, with persistent and non-uniform enhancement observed throughout the portal vein and
[1,2]
delayed phases, surpassing the enhancement seen in the liver parenchyma . It is important to note,
however, that at the imaging level, ICC cannot be reliably differentiated from HCC . Categorized into three
[1]
types based on anatomical location (intrahepatic, perihilar, and distal), cholangiocarcinoma exhibits
[3,4]
heterogeneity . Among them, intrahepatic cholangiocarcinoma (ICC) exhibits notable heterogeneity, with
tumors resembling either conventional mucinous adenocarcinomas (large duct type) or transformed
[5]
interlobular bile ducts (small duct type) . While the most common risk factors for ICC differ between
Western regions, where primary sclerosing cholangitis predominates, and Eastern regions, where parasitic
[4,6]
infections are prevalent, the incidence has been similarly increasing in recent years . Although radical
surgical excision remains the only curative option for ICC, its efficacy is limited. The 5-year post-surgery
survival rate for patients is approximately 30%, with a high recurrence rate of 60%-70% within five years
[7-9]
post-surgery . What is worse, over 70% of patients with ICC are diagnosed with advanced-stage ICC,
characterized by either local infiltration or distant metastasis [10,11] . This subgroup of patients has a poor
[11]
prognosis and does not meet the criteria for surgery, compelling a shift towards systematic therapy .
The management of ICC typically relies on patient-specific and tumor-specific factors, and treatment
decisions often involve multimodal therapy ideally determined by a multidisciplinary team of experts. This
team selects patients for surgical resection, perioperative chemotherapy, transplantation, systemic therapies,
and so on. While gemcitabine-cisplatin (GEMCIS) chemotherapy has provided significant relief as a first-
line treatment in systemic therapies , single GEMICS therapy showed limitations in the coming age of
[12]
precision medicine. The introduction of immunotherapy has significantly transformed the treatment
[10]
approach for cholangiocarcinoma over the years, providing renewed hope . One notable advancement is
the introduction of durvalumab, a powerful antibody that inhibits the programmed cell death-ligand 1 (PD-
L1), into the realm of first-line treatments [13,14] . This therapy has shown significant efficacy and offers new
possibilities for patients with advanced ICC. Additionally, in contrast to HCC, the study of gene mutation-
based therapies in ICC has progressed rapidly. Several drugs targeting specific gene mutations have received
FDA approval as second-line treatment options [15-17] . These options provide a fresh outlook for patients who
cannot tolerate first-line chemotherapy or have developed resistance, especially for those with specific gene
mutations.

The gold standard for confirming ICC typically involves conducting a pathology examination after a biopsy,
and treatment is initiated upon confirmation of the diagnosis. However, given the absence of histologic
markers indicating specific biological behavior, such as aggressiveness, the utilization of genetic testing to
[18]
identify targeted drugs becomes crucial for achieving efficient personalized treatment . The introduction
of next-generation sequencing (NGS) has revolutionized genomic profiling technologies, allowing for
advanced analysis of genetic information , providing valuable insights into initiation, progression, and
[19]
treatment resistance mechanisms in ICC. These technologies have enabled the identification of specific
genetic alterations, unveiling new possibilities for the progression of innovative intervention methods. In
ICC, several actionable targets were discovered, with fibroblast growth factor receptors (FGFRs) being of
particular interest [10,20,21] . Numerous tyrosine kinase inhibitors targeting FGFRs are currently undergoing