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Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions

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Abstract

Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer. Some CDK4/6i drugs are also able to cross the blood brain barrier and may, therefore, offer effective therapy for primary and metastatic central nervous system malignancies. Ongoing research is also evaluating CDK4/6i for additional breast cancer subtypes and non-breast malignancies with promising early phase clinical trial results. Finally, pre-clinical research has identified potential biomarkers for CDK4/6i efficacy and is exploring potential resistance mechanisms to this treatment. Further clinical-translational research is needed to advance patient selection and combinatorial treatment strategies with CDK4/6i in breast cancer and other malignancies.

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Authors and Affiliations

  1. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd; Z6.2030, Houston, TX, 77030, USA

    Smruthi Vijayaraghavan

  2. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354; CPB5.3542, Houston, TX, 77030, USA

    Stacy Moulder

  3. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd., Unit 0066; Z6.3012, Houston, TX, 77030, USA

    Khandan Keyomarsi

  4. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030-4009, USA

    Rachel M. Layman

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  1. Smruthi Vijayaraghavan
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  2. Stacy Moulder
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  3. Khandan Keyomarsi
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  4. Rachel M. Layman
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Correspondence to Rachel M. Layman.

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Conflict of Interest

Dr. Layman has received <$5000 in consulting fees from Novartis and currently receives research funding from Pfizer and Novartis as Principal Investigator for ongoing clinical trials at her institution.

Dr. Moulder has received <$10,000 in consulting fees from Novartis. Dr. Moulder currently receives research funding from Pfizer and Novartis as Principal Investigator for ongoing clinical trials at her institution.

The other authors declare no conflict of interest.

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Vijayaraghavan, S., Moulder, S., Keyomarsi, K. et al. Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions. Targ Oncol 13, 21–38 (2018). https://doi.org/10.1007/s11523-017-0541-2

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