Cholangiocarcinoma (CCA)
Cholangiocarcinoma (CCA), also known as bile duct cancer, is a rare and aggressive malignancy that arises from the cells lining the bile ducts. Our company is at the forefront of CCA drug and therapy development services, aiming to provide you with a one-stop solution.
Overview of CCA
Cholangiocarcinoma (CCA) is a rare cancer originating in the bile ducts, responsible for transporting bile from the liver to the small intestine. Its overall incidence is less than 2 per 100,000. This malignant tumor can manifest anywhere along the bile ducts, including intrahepatic (within the liver), perihilar (at the junction where the bile ducts exit the liver), or distal (outside the liver). Based on its anatomical location, cholangiocarcinoma can be classified into three primary subtypes:
- Intrahepatic Cholangiocarcinoma (iCCA)
- Perihilar Cholangiocarcinoma (pCCA)
- Distal Cholangiocarcinoma (dCCA)
Fig.1 Anatomic subtypes of CCA. (Brindley, Paul J., et al., 2021)Pathogenesis of CCA
Recent advancements in molecular understanding have shed light on key mutations and molecular biomarkers associated with CCA.
- The most commonly identified mutations in CCA are isocitrate dehydrogenase isoenzyme (IDH1) and KRAS. Mutations in IDH1, present in approximately 15-25% of CCA tumors, lead to the production of oncometabolite 2-hydroxyglutarate (2-HG), promoting oncogenesis. KRAS mutations are also frequently observed and contribute to tumor progression.
- Moreover, fibroblast growth factor receptor 2 (FGFR2) fusions are found in a subset of intrahepatic CCA (IHCC) cases. These fusions represent an attractive therapeutic target, and inhibitors like infigratinib have shown promising activity in CCA research.
Targets of CCA Therapy
Apart from IDH1 and KRAS, other molecular targets have been explored for CCA therapy development.
Epidermal growth factor receptors (EGFR) and HER2/neu receptors, which harbor erbB2 mutations, have received attention. Inhibitors such as erlotinib and cetuximab have shown some efficacy, either as monotherapy or in combination with cytotoxic therapy.
The presence of HER2 mutations in CCA is associated with a worse prognosis. Ongoing trials are investigating the efficacy of HER2 targeting agents in different types of CCA, including perihilar and distal CCA.
Mutations in the AKT/mTOR pathway have also been identified in CCA, indicating their potential as therapeutic targets. However, trials with AKT inhibitors have shown limited efficacy, highlighting the need for further research and development in this area.
Therapy Development of CCA
- Immunotherapy
Immunotherapy has emerged as a promising approach for various cancers, including CCA. Immune checkpoint blockade, which targets molecules like PD-1/PD-L1, has shown activity in a subset of CCA with mismatch repair deficiency or microsatellite instability-high (MSI-H) tumors.
- Targeted Therapy
Targeted therapies aim to specifically inhibit the molecular drivers of CCA. As mentioned earlier, inhibitors targeting IDH1, such as ivosidenib (AG-120), have shown promise in trials, with some cases experiencing stable disease or partial response.
Fig.2 Evolving molecular stratification of CCA and therapeutic implications. (Rizvi, Sumera, et al., 2018)Our Services
Our company is dedicated to accelerating CCA therapy development through our extensive range of services, including drug development, diagnostics development, therapy development, and animal model development. Our expertise and state-of-the-art facilities make us a leader in developing innovative therapies for CCA.
Therapy Development Platforms
Animal Models of Cholangiocarcinoma (CCA)
One key aspect of advancing CCA research is the development of reliable animal models that accurately mimic the biological and pathological characteristics of human CCA. Our company is at the forefront of providing comprehensive CCA animal model development services.
| Chemotoxic-Induced Models | |||
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| Chemotoxic-induced models involve the administration of chemical agents to induce CCA in animals. This approach enables the study of the carcinogenic effects of specific compounds or the recapitulation of risk factors associated with CCA development. | |||
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| Genetically Engineered Models | |||
| By manipulating specific genes involved in CCA pathogenesis, we can create models that closely resemble the disease's molecular and histopathological characteristics. One notable example of our genetically engineered CCA models involves the liver-specific deletion of Smad4 and Pten, two tumor suppressor genes frequently mutated in CCA. | |||
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| Optional Species | Mice, Rats, Others | ||
In addition, our company offers a range of innovative model development services to cater to the diverse needs of CCA research. These services include the development of Xenograft Models and Syngeneic Models. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Brindley, Paul J., et al. "Cholangiocarcinoma." Nature reviews Disease primers 7.1 (2021): 65.
- Rizvi, Sumera, et al. "Cholangiocarcinoma—evolving concepts and therapeutic strategies." Nature reviews Clinical oncology 15.2 (2018): 95-111.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.