Klatskin tumor is a rare yet highly lethal form of cholangiocarcinoma. At Protheragen, we offer comprehensive diagnostics and therapeutics development services for Klatskin tumor, leveraging our deep scientific expertise and state-of-the-art facilities.
Overview of Klatskin Tumor
Klatskin tumor, also known as hilar cholangiocarcinoma, is a rare and aggressive malignancy that originates at the confluence of the right and left hepatic bile ducts, forming the common bile duct. This tumor is named after Gerald Klatskin, who first described its distinct clinical and pathological features in 1965. Klatskin tumors represent a significant challenge in oncology due to their late presentation, often leading to poor prognosis and low survival rates. They account for 10-20% of all intrahepatic disorders and 2% of all cancers, with a higher incidence observed among Asian and Pacific Islanders.
Fig.1 Kaplan–Meyer graph with survival differences for Klatskin tumors considering median value for inflammatory ratios: (a) survival considering NLR > median value; (b) survival considering PLR > median value. (Nechita V. I.,
et al., 2022)
Pathogenesis of Klatskin Tumor
The pathogenesis of Klatskin tumors is multifactorial, involving a combination of genetic, environmental, and inflammatory factors. Primary sclerosing cholangitis (PSC) is a significant risk factor, contributing to approximately 40% of cases. This chronic inflammatory condition of the bile ducts is characterized by diffuse fibrosis and strictures, predisposing individuals to cholangiocarcinoma. Parasitic infections, particularly with liver flukes such as Clonorchis sinensis and Opisthorchis viverrine, are prevalent in Southeast Asia and are strongly associated with Klatskin tumors. Other risk factors include cholelithiasis, fibrocystic liver diseases like Caroli's disease, exposure to toxins such as thorotrast, and chronic liver diseases. Genetic syndromes, including Lynch syndrome and biliary papillomatosis, also increase the risk of developing these tumors.
Diagnostics Development for Klatskin Tumor
Tumor markers such as CA-19-9 are commonly used in the diagnosis of Klatskin tumors. Elevated levels of CA-19-9 can indicate the presence of a tumor, although false negatives are possible. Liver function tests, including elevated liver enzymes and bilirubin levels, are indicative of biliary obstruction and are often elevated in cases with Klatskin tumors.
Histopathological Examination
Biopsy and histological analysis are crucial for confirming the diagnosis of Klatskin tumors. Tissue samples obtained through endoscopic or percutaneous methods are examined under a microscope to identify the presence of malignant cells and characterize the tumor type. This information is essential for determining the appropriate therapeutic strategy.
Therapeutics of Klatskin Tumor
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Gemcitabine |
DNA synthesis / Cell division |
Used in various settings, including adjuvant, neoadjuvant, and palliative therapy. Often used in combination with cisplatin. |
Approved |
| Cisplatin |
DNA cross-linking / Cell division |
Often combined with gemcitabine as a standard therapeutic for unresectable biliary tract cancers. |
Approved |
| Fluorouracil |
DNA synthesis / Cell division |
Mentioned as a chemotherapy agent. |
Approved |
| Capecitabine |
DNA synthesis / Cell division |
Mentioned as a chemotherapy agent. |
Approved |
| Oxaliplatin |
DNA cross-linking / Cell division |
Mentioned as a chemotherapy agent. |
Approved |
| Liposomal Irinotecan |
Topoisomerase I / DNA replication |
Mentioned as a chemotherapy agent. |
Approved |
| Targeted Therapy |
Entrectinib |
NTRK gene fusion |
Used for tumors with NTRK gene fusions. |
Approved |
| Larotrectinib |
NTRK gene fusion |
Used for tumors with NTRK gene fusions. |
Approved |
| Dabrafenib |
BRAF V600 mutation |
Used in combination with trametinib for BRAF-V600 mutated tumors. |
Approved |
| Trametinib |
MEK |
Used in combination with dabrafenib for BRAF-V600 mutated tumors. |
Approved |
| Pemigatinib |
FGFR 2 fusion/rearrangement |
Used for tumors with FGFR 2 fusions or rearrangements. |
Approved |
| Infigratinib |
FGFR 2 fusion/rearrangement |
Used for tumors with FGFR 2 fusions or rearrangements. |
Approved |
| Ivosidenib |
IDH1 mutation |
Used for tumors with IDH1 mutations. |
Approved |
| Immunotherapy |
Pembrolizumab |
PD-1 |
Used for MSI high or dMMR tumors and TMB-H tumors. |
Approved |
| Dostarlimab-gxly |
PD-1 |
Used for MSI high or dMMR tumors. |
Approved |
| Nivolumab |
PD-1 |
Can be used as a single agent or in combination (e.g., with ipilimumab) for TMB-H tumors. |
Approved |
| Ipilimumab |
CTLA-4 |
Used in combination with nivolumab for TMB-H tumors. |
Approved |
| Durvalumab |
PD-L1 |
Can be used as a single agent. |
Approved |
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
Protheragen offers comprehensive services for the development of diagnostics and therapeutics for Klatskin tumors. Our expertise spans from early-stage research to preclinical studies, providing a full spectrum of solutions tailored to meet the unique challenges of this rare malignancy.
Disease Models
- Matrigel-Based Organoids
- Decellularized ECM-Based Organoids
- Patient-Derived Xenograft (PDX) Models
- Diethylnitrosamine (DEN) Induced Models
Recognizing the unique challenges presented by Klatskin tumor and the diverse needs of our clients, Protheragen offers highly customized services. We collaborate closely with our partners to design bespoke preclinical research programs that align with their specific objectives, whether it's exploring a novel therapeutic modality, validating a new diagnostic biomarker, or addressing complex mechanistic questions. If you are interested in our services, please feel free to contact us.
References
- Nechita, Vlad-Ionuţ, et al. "Klatskin Tumor: A Survival Analysis According to Tumor Characteristics and Inflammatory Ratios." Medicina 58.12 (2022): 1788.
- Agrawal, Vartika, et al. "A Typical Case of an Atypical Disease: Klatskin Tumor." Cureus 14.9 (2022).
- Sharma, Prabin, and Siddhartha Yadav. "Demographics, tumor characteristics, treatment, and survival of patients with Klatskin tumors." Annals of gastroenterology 31.2 (2018): 231.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
