In 2021, our understanding of resistance to therapy in primary liver tumours improved drastically. By taking a holistic approach, three independent studies have characterized the tumour cell biodiversity across space, time and aetiologies in primary liver cancer, decoding the crosstalk between different cell types within the tumour ecosystem and their individual contributions to therapy resistance.
Integrated genomic analysis discovered a major role for cell plasticity in the spatio-temporal evolution of paediatric liver cancers and their resistance to cisplatin-based chemotherapy3.
Single-cell transcriptomic profiling of primary liver tumours (hepatocellular carcinoma and intra-hepatic cholangiocarcinoma) identified intra-tumoural cell states and quantified the degree of diversity, which could help to understand tumour evolution in response to treatment4.
Anti-PD1 treatment can accelerate hepatocarcinogenesis or be ineffective in the context of nonalcoholic steatohepatitis, which highlights a potential weakness of immunotherapies6.
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A.L. has received consulting fees from AstraZeneca and research funding from Genentech and Pfizer. C.D. declares no competing interests.
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Desdouets, C., Lujambio, A. Decoding therapy resistance in liver tumours: a giant leap. Nat Rev Gastroenterol Hepatol 19, 83–84 (2022). https://doi.org/10.1038/s41575-021-00550-1