Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma
Rebecca A Sager1,2, Sarah J Backe1,2,3, Elham Ahanin1,2,3
1Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA.
Abstract:
The treatment of advanced and metastatic kidney cancer has entered a golden era with the addition of more therapeutic options, improved survival and new targeted therapies. Tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors and immune checkpoint blockade have all been shown to be promising strategies in the treatment of renal cell carcinoma (RCC). However, little is known about the best therapeutic approach for individual patients with RCC and how to combat therapeutic resistance. Cancers, including RCC, rely on sustained replicative potential. The cyclin-dependent kinases CDK4 and CDK6 are involved in cell-cycle regulation with additional roles in metabolism, immunogenicity and antitumour immune response. Inhibitors of CDK4 and CDK6 are now commonly used as approved and investigative treatments in breast cancer, as well as several other tumours. Furthermore, CDK4/6 inhibitors have been shown to work synergistically with other kinase inhibitors, including mTOR inhibitors, as well as with immune checkpoint inhibitors in preclinical cancer models. The effect of CDK4/6 inhibitors in kidney cancer is relatively understudied compared with other cancers, but the preclinical studies available are promising. Collectively, growing evidence suggests that targeting CDK4 and CDK6 in kidney cancer, alone and in combination with current therapeutics including mTOR and immune checkpoint inhibitors, might have therapeutic benefit and should be further explored.
Insights
Targeting cyclin-dependent kinases CDK4 and CDK6 shows promise for advanced kidney cancer treatment. Combining CDK4/6 inhibitors with existing therapies like mTOR inhibitors and immune checkpoint inhibitors may improve outcomes and overcome resistance.
Area of Science:
- Oncology
- Cancer Therapeutics
- Molecular Biology
Background:
- Advanced and metastatic kidney cancer (renal cell carcinoma, RCC) treatment has advanced with targeted therapies and immunotherapies.
- Challenges remain in personalized treatment approaches and overcoming therapeutic resistance in RCC.
- Cyclin-dependent kinases CDK4 and CDK6 play crucial roles in cell-cycle regulation, metabolism, and immune response in cancer.
Purpose of the Study:
- To explore the potential therapeutic benefit of targeting cyclin-dependent kinases CDK4 and CDK6 in kidney cancer.
- To investigate the efficacy of CDK4/6 inhibitors alone and in combination with existing RCC treatments.
Main Methods:
- Review of preclinical studies on CDK4/6 inhibitors in kidney cancer.
- Analysis of the role of CDK4/6 in cancer cell proliferation, metabolism, and immune interactions.
- Examination of synergistic potential with mTOR inhibitors and immune checkpoint inhibitors.
Main Results:
- Preclinical data suggest CDK4/6 inhibitors have a promising effect in kidney cancer models.
- CDK4/6 inhibitors demonstrate synergistic effects with other kinase inhibitors and immune checkpoint inhibitors in preclinical settings.
- The role of CDK4/6 in kidney cancer remains relatively understudied compared to other malignancies.
Conclusions:
- Targeting CDK4 and CDK6, alone or in combination with current therapies, may offer therapeutic benefits for kidney cancer patients.
- Further research into CDK4/6 inhibitors is warranted to explore their efficacy and optimal use in renal cell carcinoma treatment.
- CDK4/6 inhibition presents a potential strategy to combat therapeutic resistance in advanced kidney cancer.
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