A clinical evaluation of treatments that target cell cycle machinery in breast cancer

ABSTRACT

Introduction: The dysregulation of cell cycle control can lead to cancer development. In breast cancer, cyclin D, CDK 4,6 and the retinoblastoma protein play a central role in the control of cell proliferation, in crosstalk with the estrogen receptor and Her2 pathways. Although the mechanisms by which the CDK4/6 complex is involved in the control of cell growth in triple negative breast cancer (TNBC) are still unclear, some TNBCs might be sensitive to CDK4/6 inhibitors.

Areas covered: The authors provide an overview of the treatments that target cell cycle machinery in breast cancer and provide their perspectives for the future.

Expert opinion: CDK 4/6 inhibitors are active drugs in HR+ MBC, but some unresolved issues remain. We need to identify biomarkers of response. Moreover, we need to determine the optimal timing for the incorporation of CDK 4/6 inhibitors in the current treatment algorithm. In the Her2 positive subtype, the triple combination of anti Her2 therapies with CDK4/6 inhibitors and endocrine therapy seems to be a promising chemotherapy free approach. Efforts must still be made for the treatment of the TNBC subtype, even though new CDK 4/6 combinations are emerging as promising approaches to selected patients.

KEYWORDS:

• CDK4/6 inhibitors
• cell cycle
• targeted treatment
• triple negative breast cancer
• Her2 positive breast cancer
• HR+ breast cancer

Article highlights

• The dysregulation of the cell cycle control mechanisms determines the alteration of cell growth and contributes to the uncontrolled proliferation characteristic of cancer.

• In breast cancer cyclin D, CDK 4,6 and the retinoblastoma protein play a central role in the control of cell proliferation, in the crosstalk with the estrogen receptor and Her2 signaling pathways.

• TNBC seems to be highly sensitive to CDK in vivo, but the biological rationale is unknown.

• The strategy of targeting the cell cycle machinery, through CDK 4/6 inhibitors, is emerging as a promising treatment across all the three subtypes of breast cancer.

• We await the results of the many studies in progress with new combinations of CDK4/6 to better tailor the treatment with these new targeted agents.

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Acknowledgments

We thank Ms Antonio Guadalupi for support and assistance with the preparation of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.