The importance of preclinical models for cholangiocarcinoma drug discovery DOI
Florian Primavesi, Felix J. Krendl, Rupert Oberhuber

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- extrahepatic biliary system (intrahepatic cholangiocarcinoma) gallbladder with common feature poor prognosis, despite increasing molecular knowledge associated genetic aberrations possible targeted therapies. Therefore, search for even more precise individualized therapies is ongoing preclinical tumor models are central to development such new approaches. The described in current review include simple advanced vitro vivo models, including cell lines, 2D monolayer, spheroid organoid cultures, 3D bioprinting, patient-derived xenografts, recently, machine-perfusion platform-based resected liver specimens. All these have individual advantages, disadvantages limitations that need be considered depending on desired application. In addition potential cost limitations, availability BTC types, time required model establishment growth success rate, differently reflect relevant characteristics as heterogeneity, spatial tumor-stroma microenvironment interactions, metabolic nutritional gradients immunological interactions. consequent combination different may improve clinical study outcomes by strengthening data basis.

Language: Английский

The importance of preclinical models for cholangiocarcinoma drug discovery DOI
Florian Primavesi, Felix J. Krendl, Rupert Oberhuber

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- extrahepatic biliary system (intrahepatic cholangiocarcinoma) gallbladder with common feature poor prognosis, despite increasing molecular knowledge associated genetic aberrations possible targeted therapies. Therefore, search for even more precise individualized therapies is ongoing preclinical tumor models are central to development such new approaches. The described in current review include simple advanced vitro vivo models, including cell lines, 2D monolayer, spheroid organoid cultures, 3D bioprinting, patient-derived xenografts, recently, machine-perfusion platform-based resected liver specimens. All these have individual advantages, disadvantages limitations that need be considered depending on desired application. In addition potential cost limitations, availability BTC types, time required model establishment growth success rate, differently reflect relevant characteristics as heterogeneity, spatial tumor-stroma microenvironment interactions, metabolic nutritional gradients immunological interactions. consequent combination different may improve clinical study outcomes by strengthening data basis.

Language: Английский

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