Concepedia

Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Sandro Nuciforo, Isabel Fofana, Matthias S. Matter, Tanja Blumer, Diego Calabrese, Tujana Boldanova, Salvatore Piscuoglio, Stefan Wieland, Femke Ringnalda, Gerald Schwank,

Cell Reports · 2018 · 465 citations · 43 references

DOI Full text

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Concepts

MedicineOncologyPharmacologyCancer PharmacologyMolecular OncologyTranslational OncologyHepatobiliary CancerHepatocellular CarcinomaLiver CancerMalignant NeoplasmsPreclinical Cancer ModelsCancer OrganoidsHepatic Cell Culture ModelsIntratumor Genetic HeterogeneityMultikinase InhibitorsOrganoidsPrimary Liver CancerSorafenib TherapyTumor Organoid Models

TL;DR

Hepatocellular carcinoma is the most common primary liver cancer, and its treatment with sorafenib is limited by heterogeneity, adverse effects, and resistance, while existing in vitro models fail to capture key tumor features. The study aims to generate long‑term organoid cultures from tumor needle biopsies of HCC patients across etiologies and stages. Organoids were established by culturing biopsy‑derived tumor cells under conditions that support sustained growth, preserving morphology and marker expression. The resulting organoids preserved tumor morphology, marker expression, and genetic heterogeneity, and demonstrated sensitivity to sorafenib, indicating their utility for personalized therapy development.

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second most frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib is the only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients and is limited due to adverse effects and drug resistance. Current in vitro models fail to recapitulate key features of HCCs. We report the generation of long-term organoid cultures from tumor needle biopsies of HCC patients with various etiologies and tumor stages. HCC organoids retain the morphology as well as the expression pattern of HCC tumor markers and preserve the genetic heterogeneity of the originating tumors. In a proof-of-principle study, we show that liver cancer organoids can be used to test sensitivity to sorafenib. In conclusion, organoid models can be derived from needle biopsies of liver cancers and provide a tool for developing tailored therapies.