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Translational Therapeutics

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer

British Journal of Cancer volume 130, pages 1239–1248 (2024)Cite this article

Subjects

Abstract

BACKGROUND

Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies.

Methods

In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer.

Results

Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging.

Conclusion

CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

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Fig. 1: CDK7 is a critical regulator of transcription.
Fig. 2: CDK7 phosphorylates the CTD of RNA polymerase II (RNA Pol II) at serine 5 and serine 7 to regulate the initiation of transcription and promoter escape.
Fig. 3: As a component of the general transcription factor complex TFIIH, CDK7 regulates estrogen receptor (ER) activity.
Fig. 4: CDK7 activity is required for the expression of numerous genes involved in TNBC.

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Data availability

We declare that the materials described in the manuscript, including all relevant figures, are freely available to any scientist wishing to use them for noncommercial purposes, without breaching participant confidentiality.

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Funding

Zhaoyang project, Guangdong Provincial Hospital of Chinese Medicine

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Authors and Affiliations

  1. Department of Breast Cancer, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China

    Xue Song, Chen Fang, Yan Dai, Yang Sun, Chang Qiu, Xiaojie Lin & Rui Xu

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  1. Xue Song
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  2. Chen Fang
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  3. Yan Dai
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  4. Yang Sun
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  5. Chang Qiu
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  6. Xiaojie Lin
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  7. Rui Xu
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Contributions

Xue Song: Conceptualization and writing. Chen Fang: Revision. Yang Sun, Xiaojie Lin and Yan Dai: Resources and literature search. Chang Qiu: Picture drawing. Rui Xu: Reviewing and Editing. All authors read and approved the manuscript.

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Correspondence to Rui Xu.

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Song, X., Fang, C., Dai, Y. et al. Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer. Br J Cancer 130, 1239–1248 (2024). https://doi.org/10.1038/s41416-024-02589-8

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  • DOI: https://doi.org/10.1038/s41416-024-02589-8

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