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Accelerating Liver Cancer Research with Three Dimensional Tumoroids

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Review of “Human primary liver cancer–derived organoid cultures for disease modeling and drug screening” from Nature Medicine by Stuart P. Atkinson

While many studies aim to discover the next anti-cancer wonder drug, we still currently lack adequate in vitro models to thoroughly test the effectiveness of new treatments. Much analysis has relied on traditional two-dimensional cancer cell culture and mouse xenograft models; however, in vitro 3D culture systems derived from primary cells or pluripotent stem cells known as organoids hold the potential to revolutionize cancer studies. A new study from the laboratory of Meritxell Huch (University of Cambridge, Cambridge, UK) now describes the development of liver cancer organoids, or tumoroids, as faithful models with the potential to significantly accelerate liver cancer research [1]. 

The current Nature Medicine report comes after the establishment of the culture conditions necessary for the long-term expansion of healthy-liver derived cells [2, 3], which the authors employed to propagate cancer cells derived from patients with three common cancer subtypes (hepatocellular carcinoma, cholangiocarcinoma, and combined tumors). Resultant liver cancer tumoroids displayed several important characteristics not observed for any liver cancer cell line grown in 2D: 3D tumoroids maintained the histological architecture, gene expression patterns, and genetic makeup of the original parent tumor even after long-term in vitro expansion (~1 year). Furthermore, xenograft studies in immunocompromised mice also indicated that long-term cultured liver tumoroids maintained the tumorigenic potential, histological features, and metastatic properties of the parental tumors.

But what are the potential applications of liver tumoroids? Transcriptomic comparisons enabled the authors to establish a list of common liver tumoroid genes that may represent potential prognostic biomarkers for primary liver cancer, while the study also highlighted their suitability for biomarker identification and drug-screening testing. Encouragingly, this realization led to the identification of an ERK inhibitor as a potentially exciting new liver cancer treatment.

Liver cancer tumoroids represent a quick, easy, and reliable model system to accelerate liver cancer research; can other cancer studies take advantage of this strategy to identify new biomarkers, test new drugs, and create personalized cancer therapies? Stay tuned to the Stem Cells Portal to find out!

References

  1. Broutier L, Mastrogiovanni G, Verstegen MM, et al., Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med 2017;23:1424-1435.
  2. Huch M, Gehart H, van Boxtel R, et al., Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 2015;160:299-312.
  3. Broutier L, Andersson-Rolf A, Hindley CJ, et al., Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat Protoc 2016;11:1724-43.