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Translational Therapeutics

FGFR4-driven plasticity in breast cancer progression and resistance to therapy

British Journal of Cancer (2024)Cite this article

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Abstract

Breast cancer (BCa) is a complex and heterogeneous disease, with different intrinsic molecular subtypes that have distinct clinical outcomes and responses to therapy. Although intrinsic subtyping provides guidance for treatment decisions, it is now widely recognised that, in some cases, the switch of the BCa intrinsic subtype (which embodies cellular plasticity), may be responsible for therapy failure and disease progression. Aberrant FGFR4 signalling has been implicated in various cancers, including BCa, where it had been shown to be associated with aggressive subtypes, such as HER2-enriched BCa, and poor prognosis. More importantly, FGFR4 is also emerging as a potential driver of BCa intrinsic subtype switching, and an essential promoter of brain metastases, particularly in the HER2-positive BCa. Although the available data are still limited, the findings may have far-reaching clinical implications. Here, we provide an updated summary of the existing both pre- and clinical studies of the role of FGFR4 in BCa, with a special focus on its contribution to subtype switching during metastatic spread and/or induced by therapy. We also discuss a potential clinical benefit of targeting FGFR4 in the development of new treatment strategies.

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Fig. 1: Schematic overview of FGFR4 contribution to BCa progression, resistance to anti-HER2 therapies, and site-specific metastases.
Fig. 2: FGFR4 alterations and mRNA levels in breast cancer.

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Acknowledgements

Figure 1 was created with BioRender.com.

Funding

This research was funded by the Polish National Science Centre grant OPUS no. 2020/39/B/NZ4/02696 (to HMR), PRELUDIUM no. 2018/29/N/NZ4/02384, LIDER no. 0188/L-13/2022 (to MB), Sonata Bis no. UMO-2018/30/E/NZ3/00222 (to RS).

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  1. These authors contributed equally: Marcin Braun, Dominika Piasecka.

Authors and Affiliations

  1. Department of Pathology, Chair of Oncology, Medical University of Lodz, Lodz, Poland

    Marcin Braun & Hanna M. Romanska

  2. Laboratory of Molecular Enzymology and Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdansk, Gdansk, Poland

    Dominika Piasecka & Rafal Sadej

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  1. Marcin Braun
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MB and DP reviewed literature, drafted the manuscript and prepared the figures. MB, DP, RS and HMR conceived the study. RS and HMR supervised the study and revised the manuscript. All Authors read and approved the final version of manuscript.

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Correspondence to Rafal Sadej or Hanna M. Romanska.

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Braun, M., Piasecka, D., Sadej, R. et al. FGFR4-driven plasticity in breast cancer progression and resistance to therapy. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02658-y

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