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Targeting the RB-E2F pathway in breast cancer

Oncogene volume 35, pages 4829–4835 (2016)Cite this article

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Abstract

Mutations of the retinoblastoma tumor-suppressor gene (RB1) or components regulating the CDK-RB-E2F pathway have been identified in nearly every human malignancy. Re-establishing cell cycle control through cyclin-dependent kinase (CDK) inhibition has therefore emerged as an attractive option in the development of targeted cancer therapy. The most successful example of this today is the use of the CDK4/6 inhibitor palbociclib combined with aromatase inhibitors for the treatment of estrogen receptor-positive breast cancers. Multiple studies have demonstrated that the CDK-RB-E2F pathway is critical for the control of cell proliferation. More recently, studies have highlighted additional roles of this pathway, especially E2F transcription factors themselves, in tumor progression, angiogenesis and metastasis. Specific E2Fs also have prognostic value in breast cancer, independent of clinical parameters. We discuss here recent advances in understanding of the RB-E2F pathway in breast cancer. We also discuss the application of genome-wide genetic screening efforts to gain insight into synthetic lethal interactions of CDK4/6 inhibitors in breast cancer for the development of more effective combination therapies.

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Acknowledgements

The work of RB and LFAW is supported by grants of The Dutch Cancer Society and the and by the Cancer Genomics Netherlands consortium. MG’s work is supported by the Wellcome Trust (102696), the Dutch Cancer Society (H1/2014-6919), Stand Up 2 Cancer and a European Research Council Synergy grant.

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Authors and Affiliations

  1. Division of Molecular Carcinogenesis and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    J Johnson, B Thijssen, L F A Wessels & R Bernards

  2. Wellcome Trust Sanger Institute, Cambridge, UK

    U McDermott & M Garnett

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Correspondence to R Bernards.

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Johnson, J., Thijssen, B., McDermott, U. et al. Targeting the RB-E2F pathway in breast cancer. Oncogene 35, 4829–4835 (2016). https://doi.org/10.1038/onc.2016.32

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