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Recent Advances of Cell-Cycle Inhibitor Therapies for Pediatric Cancer
Christopher C Mills1, E A Kolb2, Valerie B Sampson3
1University of Delaware, Newark, Delaware.
Cancer Research
|November 4, 2017
Summary
This review explores cell-cycle inhibitors for pediatric cancer, detailing drugs targeting CDK4/CDK6, aurora kinases, Wee1 kinase, KSP, and tubulin. Pediatric-focused development is crucial for advancing treatments for rare childhood cancers.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cell-cycle and checkpoint regulators are critical in cancer development.
- Targeting these regulators offers a promising therapeutic strategy for various cancers.
- Pediatric cancers often differ from adult cancers, necessitating specific drug development approaches.
Purpose of the Study:
- To review the roles of cell-cycle and checkpoint regulators in pediatric cancer.
- To discuss the development of specific cell-cycle inhibitors for therapeutic use in children.
- To highlight the importance of mechanism-based combinations and pediatric-focused drug development.
Main Methods:
- Review of existing literature on cell-cycle inhibitors.
- Analysis of drug mechanisms of action, safety, and tolerability in pediatric patients.
- Discussion of drug development strategies for rare childhood diseases.
Main Results:
- Pivotal roles of cell-cycle and checkpoint regulators identified.
- Specific inhibitors targeting CDK4/CDK6 (palbociclib, ribociclib, abemaciclib), aurora kinases (AT9283, MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids) discussed.
- Safety and tolerability data in pediatric patients presented.
Conclusions:
- Cell-cycle inhibitors show potential for pediatric cancer therapy.
- Mechanism-based drug combinations are essential for exploiting signaling pathways.
- Pediatric-focused drug development is critical for advancing treatments for rare childhood diseases.
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