Cyclin-Dependent Kinase Inhibition in Prostate Cancer: Past, Present, and Future
Matthew Siskin1, Minas P Economides1, David R Wise1
1Genitourinary Medical Oncology Service, Perlmutter Cancer Center, NYU Langone Heath Center, New York, NY 10016, USA.
Background:
Despite significant progress, prostate cancer remains a leading cause of death. Cyclin-dependent kinase (CDK) 4/6 inhibitors, which are already approved for the treatment of hormone receptor-positive breast cancer, are undergoing extensive testing as monotherapy and in various combinations as a potentially valuable treatment modality in prostate cancer patients. Thus far, a limited number of these studies have published results, which have been largely disappointing.
Areas Covered:
In this review, we describe the biologic rationale for the use of CDK4/6 inhibitors in prostate cancer, the existing clinical data describing their use in prostate cancer, and ongoing clinical trials of CDK4/6 inhibitors as monotherapy and in combination for the treatment of prostate cancer. In particular, we focus on possible resistance mechanisms that may be particularly relevant in prostate cancer patients, leading to de novo and acquired resistance, and we highlight novel strategies that can overcome this resistance.
Conclusions:
Current clinical trials are actively working to (1) refine the role of CDK4/6 inhibitors in prostate cancer patients; (2) develop new inhibitors of other cell-cycle targets, such as CDK2 and CDK7; and (3) explore novel combination therapies with inhibitors of other relevant pathways, such as PI3K or MAPK. Further genomic subtyping of advanced prostate cancer will likely shed light on the subsets of patients most likely to benefit from cell-cycle-targeted agents.
Insights
Cyclin-dependent kinase (CDK) 4/6 inhibitors show promise for prostate cancer, but early results are disappointing. Research is ongoing to overcome resistance and identify patient subsets who will benefit most from these cell-cycle targeted agents.
Area of Science:
- Oncology
- Cancer Therapeutics
- Prostate Cancer Research
Background:
- Prostate cancer is a significant cause of mortality despite advances in treatment.
- Cyclin-dependent kinase (CDK) 4/6 inhibitors, successful in breast cancer, are being investigated for prostate cancer.
- Initial clinical trial results for CDK4/6 inhibitors in prostate cancer have been largely disappointing.
Purpose of the Study:
- To review the biological rationale for using CDK4/6 inhibitors in prostate cancer.
- To summarize existing clinical data and ongoing trials of CDK4/6 inhibitors in prostate cancer.
- To explore resistance mechanisms and strategies to overcome them in prostate cancer patients.
Main Methods:
- Review of biological rationale for CDK4/6 inhibitors in prostate cancer.
- Analysis of existing clinical data for CDK4/6 inhibitors in prostate cancer.
- Examination of ongoing clinical trials and resistance mechanisms.
Main Results:
- Limited published results from initial studies have been largely disappointing.
- Understanding resistance mechanisms is crucial for effective treatment.
- Novel strategies are being developed to overcome resistance.
Conclusions:
- Ongoing trials aim to refine the role of CDK4/6 inhibitors in prostate cancer.
- Development of new inhibitors targeting other cell-cycle proteins (e.g., CDK2, CDK7) is underway.
- Combination therapies and genomic subtyping are key to identifying patient subsets likely to benefit from cell-cycle targeted agents.
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