Multifocal Intrahepatic Cholangiocarcinoma (ICC) is a rare yet highly aggressive form of primary liver cancer that originates from the epithelial cells lining the intrahepatic bile ducts. Protheragen provides all-encompassing services for the diagnostics and therapeutics development of ICC, harnessing state-of-the-art technologies and a wealth of scientific expertise.
Overview of Multifocal Intrahepatic Cholangiocarcinoma (ICC)
Multifocal Intrahepatic Cholangiocarcinoma (ICC) is a rare yet highly aggressive type of liver cancer that arises from the epithelial cells of the intrahepatic bile ducts. This cancer is marked by the presence of multiple tumor foci within the liver, which can significantly complicate therapeutic efforts and worsen prognosis. As the second most common primary liver cancer, ICC is seeing a rising incidence rate globally. It mainly affects people in their 50s to 70s and is more common in certain regions due to specific risk factors. These include primary sclerosing cholangitis (PSC), hepatitis B and C infections, liver cirrhosis, and parasitic infections such as Opisthorchis viverrini and Clonorchis sinensis.
Fig.1 Heat map of copy number alterations (CNAs) for multiple samples in each patient with multifocal IHC. (Lee S. H.,
et al., 2021)
Pathogenesis of Multifocal Intrahepatic Cholangiocarcinoma (ICC)
The pathogenesis of ICC is multifactorial, involving a combination of genetic, environmental, and lifestyle factors. Chronic inflammation of the bile ducts, often due to conditions like PSC, plays a significant role in the development of ICC. Genetic mutations in oncogenes and tumor suppressor genes, such as IDH1/2, FGFR2, and TP53, are frequently observed in ICC tumors. These mutations can lead to uncontrolled cell proliferation and resistance to apoptosis. Additionally, exposure to carcinogens and chronic viral infections can further contribute to the development of ICC.
Diagnostics Development for Multifocal Intrahepatic Cholangiocarcinoma (ICC)
Molecular Diagnostics
Molecular diagnostics involve the analysis of genetic mutations and biomarkers in ICC. Next-generation sequencing (NGS) technologies are employed to identify specific genetic alterations in tumor samples, which can guide targeted therapies. For instance, the identification of FGFR2 fusions and IDH1/2 mutations can inform the use of specific inhibitors. Additionally, liquid biopsies, which analyze circulating tumor DNA (ctDNA) in the blood, are being developed to provide a non-invasive diagnostic option.
Histopathological Analysis
Histopathological examination of tissue samples remains a cornerstone of ICC diagnosis. Biopsies obtained through fine-needle aspiration or surgical resection are analyzed to determine the presence of malignant cells and to classify the tumor type. Immunohistochemical staining is used to identify specific markers, such as CK7, CK19, and MUC1, which are characteristic of ICC. Advanced techniques like in situ hybridization can also be employed to detect specific genetic alterations within the tumor cells.
Therapeutics Development for Multifocal Intrahepatic Cholangiocarcinoma (ICC)
Systemic therapies, encompassing chemotherapy, targeted therapies, and immunotherapies, play a crucial role in managing ICC. Gemcitabine and cisplatin are frequently employed chemotherapeutic agents, and combinations such as gemcitabine-oxaliplatin have shown potential in clinical trials. Targeted therapies like FGFR2 inhibitors (e.g., pemigatinib) and IDH1 inhibitors (e.g., ivosidenib) have proven effective in patients with specific genetic mutations. Immunotherapies, including PD-1 inhibitors (e.g., pembrolizumab and nivolumab), are being investigated for their ability to boost the immune response against ICC.
Table 1. Ongoing trials for adjuvant and neoadjuvant therapy. (Krenzien F., et al., 2022)
| Protocol |
Trial ID |
Estimated Enrollment |
Status |
Estimated Study Completion |
| Toripalimab (PD1) +Lenvatinib vs. Gemox+Lenvatinib in for nonesectable intrahepatic cholangiocarcinoma |
NCT04361331 Huang Xiaoyong, Shanghai |
60 |
recruiting |
Dec-21 |
| Adjuvant Chemotherapy with Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer (ACTICCA-1) |
NCT02170090 University Medical Center Hamburg, Germany |
781 |
recruiting |
Apr-22 |
| Derazantinib in Subjects with FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma |
NCT03230318 Phoenix, Arizona, United States Mayo Clinic |
143 |
recruiting |
Jun-22 |
| Study of the Combination of DKN-01 and Nivolumab in Previously Treated Patients with Advanced Biliary Tract Cancer (BTC) |
NCT04057365 Massachusetts General Hospital, USA |
30 |
recruiting |
Aug-22 |
| Anti-PD1 Antibody Toripalimab Combined with Gemox as First-line Therapy in Late-stage Intrahepatic Cholangiocarcinoma |
NCT04961788 Shanghai Zhongshan Hospital |
30 |
recruiting |
Dec-22 |
| PD1 Antibody (Toripalimab), GEMOX and Lenvatinib vs. no neoadjuvant chemotherapy for resectable intrahepatic cholangiocarcinoma With High-risk Recurrence Factors |
NCT04961788 Shanghai Zhongshan Hospital |
128 |
recruiting |
Aug-23 |
| Phase Ib/II Single-arm Study of mFOLFOX6, Bevacizumab and Atezolizumab in Advanced Biliary Tract Cancer (COMBATBIL) |
NCT05052099 University Hospital, Essen, Germany |
35 |
recruiting |
Jun-24 |
| Durvalumab and Tremelimumab with Platinum-based Chemotherapy in Intrahepatic Cholangiocarcinoma (ICC) |
NCT04989218 University of Alabama at Birmingham |
20 |
Not yet recruiting |
Oct-24 |
| Durvalumab in Combination With a CSF-1R Inhibitor (SNDX-6532) Following Chemo or Radio-Embolization for Patients with Intrahepatic Cholangiocarcinoma |
NCT04301778 Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States |
30 |
recruiting |
Sep-25 |
| Neoadjuvant Chemotherapy with Gemcitabine Plus Cisplatin Followed by Radical Liver Resection Versus Immediate Radical Liver Resection Alone with or Without Adjuvant Chemotherapy in Front of Radical Resection of BTC (GAIN) |
NCT03673072 Krankenhaus Nordwest, Frankfurt Germany |
300 |
recruiting |
Nov-24 |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Harnessing state-of-the-art technologies and a wealth of scientific expertise, Protheragen provides all-encompassing services for the diagnostics and therapeutics development of ICC. Our offerings include sophisticated molecular diagnostics, in-depth histopathological analysis, as well as the creation of targeted therapies and immunotherapies.
Disease Models
- HuCCT1 Cell Lines
- RBE Cell Lines
- Adult Liver Organoids
- Chemotoxic-Induced Models
- Alb-Cre, Smad4flox/flox, Ptenflox/flox Models
Protheragen's diagnostics and therapeutics development services are distinguished by their scientific precision, innovative spirit, and client-centric philosophy. Our interdisciplinary team of specialists, with profound expertise in molecular biology, pathology, and preclinical research, is committed to delivering high-caliber and dependable outcomes. If you are interested in our services, please feel free to contact us.
References
- Lee, Sung Hwan, et al. "Genomic profiling of multifocal intrahepatic cholangiocarcinoma reveals intraindividual concordance of genetic alterations." Carcinogenesis 42.3 (2021): 436-441.
- Krenzien, Felix, et al. "Treatment of intrahepatic cholangiocarcinoma—a multidisciplinary approach." Cancers 14.2 (2022): 362.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
