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PROSTATE CANCER

Drivers of lineage plasticity

Nature Reviews Cancer volume 22, page 605 (2022)Cite this article

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The detrimental impact of cancer cell plasticity on therapy response is well documented in diverse tumour types, but the underlying mechanisms remain largely unresolved. Chan et al. now define the drivers of lineage plasticity during the progression of prostate adenocarcinomas to neuroendocrine prostate cancer (NEPC), a subtype that frequently emerges in patients with castration-resistant prostate cancer (CRPC).

By comparing scRNA-seq data of wild-type with mutant organoids, Chan et al. pinpointed plasticity onset to an early time point, when a mixed basal-luminal phenotype emerged in mutant organoids. Among gene programmes associated with plasticity, JAK–STAT and FGFR pathway activation not only preceded morphological changes but were further enriched by anti-androgen therapy, suggesting functional implication as drivers of plasticity. Indeed, pharmacological inhibition of JAK1 and JAK2 restored normal cystic morphology in fully plastic organoids, and combination treatment of a JAK and an FGFR inhibitor was even more potent.

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Original article

  • Chan, J. M. et al. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling. Science 377, 1180–1191 (2022)

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  1. Nature Reviews Cancer http://www.nature.com/nrc/

    Daniela Senft

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  1. Daniela Senft
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Correspondence to Daniela Senft.

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Senft, D. Drivers of lineage plasticity. Nat Rev Cancer 22, 605 (2022). https://doi.org/10.1038/s41568-022-00524-8

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