Animal models of cholangiocarcinoma

Ko, Kwang Suk; Peng, Jian; Yang, Heping

doi:10.1097/mog.0b013e32835d6a3e

Cited by 18 publications

(23 citation statements)

References 37 publications

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“…136 Targeting of CAFs could be an additional focus for development of new therapies and success of this approach was reported in a preclinical model using the BH3 mimetic, navitoclax. 137 Further improvement of the currently available animal models of cholangiocarcinoma 138 will be beneficial.…”

Section: Future Directionsmentioning

confidence: 99%

Cholangiocarcinoma

Razumilava¹,

Gores²

2014

The Lancet

1,518

1,314

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Cholangiocarcinoma represents a diverse group of epithelial cancers united by late diagnosis and poor outcomes. Specific diagnostic and therapeutic approaches are undertaken for cholangiocarcinomas of different anatomical locations (intrahepatic, perihilar, and distal). Mixed hepatocellular cholangiocarcinomas have emerged as a distinct subtype of primary liver cancer. Clinicians need to be aware of intrahepatic cholangiocarcinomas arising in cirrhosis and properly assess liver masses in this setting for cholangiocarcinoma. Management of biliary obstruction is obligatory in perihilar cholangiocarcinoma, and advanced cytological tests such as fluorescence in-situ hybridisation for aneusomy are helpful in the diagnosis. Liver transplantation is a curative option for selected patients with perihilar but not with intrahepatic or distal cholangiocarcinoma. International efforts of clinicians and scientists are helping to identify the genetic drivers of cholangiocarcinoma progression, which will unveil early diagnostic markers and direct development of individualised therapies.

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Section: Future Directionsmentioning

confidence: 99%

Cholangiocarcinoma

Razumilava¹,

Gores²

2014

The Lancet

1,518

1,314

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“…111 Animal models of CCA (Table 1) include mice with xenograft tumors, 43, 112–119 mice with genetic changes that lead to CCA formation, 86, 120–124 rats with orthotopic tumors 125,126 , and animals that develop CCAs following exposure to carcinogens. 55, 127–129 Although these models offer an opportunity to bridge the chasm between in vitro findings and clinical applicability, they have limitations.…”

Section: Animal Modelsmentioning

confidence: 99%

Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma

2013

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Cholangiocarcinomas (CCAs) are hepatobiliary cancers with features of cholangiocyte differentiation; they can be classified anatomically as intrahepatic (iCCA), perihilar (pCCA), or distal CCA (dCCA). These subtypes differ not only in their anatomic location but in epidemiology, origin, etiology, pathogenesis, and treatment. The incidence and mortality of iCCA has been increasing over the past 3 decades, and only a low percentage of patients survive until 5 y after diagnosis. Geographic variations in the incidence of CCA are related to variations in risk factors. Changes in oncogene and inflammatory signaling pathways, as well as genetic and epigenetic alterations and chromosome aberrations, have been shown to contribute to development of CCA. Furthermore, CCAs are surrounded by a dense stroma that contains many cancer-associated fibroblasts, which promotes their progression. We have gained a better understanding of the imaging characteristics of iCCAs and have developed advanced cytologic techniques to detect pCCAs. Patients with iCCAs are usually treated surgically, whereas liver transplantation following neoadjuvant chemoradiation is an option for a subset of patients with pCCAs. We review recent developments in our understanding of the epidemiology, pathogenesis, of CCA, along with advances in classification, diagnosis and treatment.

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“…(111) Classical models in rodents have used a carcinogen-induced model; usually diethylnitrosamine (DEN) and thioacetamide (TAA) and infection with Opistorchis viverrini . (112) Genetically-engineered mice models of cholangiocarcinoma were generated targeting TP53 , neurofibromatosis type 2 ( NF2 ), PTEN, SMAD4 and KRAS (112–114). In a transgenic mouse model, constitutive overexpression of ERBB2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma (115).…”

Section: Current Genetic Landscape and Actionable Signaturesmentioning

confidence: 99%

New Horizons for Precision Medicine in Biliary Tract Cancers

et al. 2017

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Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients presents with resectable disease; however, relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been suggested. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g. radioembolization or external beam radiation); pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next generation sequencing analyses have identified actionable mutations (e.g. FGFR fusion rearrangements and IDH-1 and -2 mutations) with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC is rapidly evolving and the subject of this review.

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Animal models of cholangiocarcinoma

Abstract: Not only establishing animal models relevant to CCA is beneficial for its early diagnosis and therapy but also well suited experimental CCA models will guide the development of applicable treatment strategy for the hard-to-cure CCA.

Cited by 18 publications

References 37 publications

Cholangiocarcinoma

Cholangiocarcinoma

Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma

New Horizons for Precision Medicine in Biliary Tract Cancers

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