Selective CDK4/6 Inhibitors: Biologic Outcomes, Determinants of Sensitivity, Mechanisms of Resistance, Combinatorial Approaches, and Pharmacodynamic Biomarkers.

Abstract

CDK4/6 inhibitors are now part of the standard armamentarium for hormone receptor-positive breast cancer. In this article, we review the biologic outcomes imposed by these drugs on cancer cells, determinants of response, mechanisms of intrinsic and acquired resistance, as well as combinatorial approaches emanating from mechanistic studies that may allow use of these agents to extend beyond breast cancer. In addition, we will address tumor-, imaging-, and blood-based pharmacodynamic biomarkers that can inform rationally designed trials as clinical development continues.

• Authors: Erik S Knudsen, Geoffrey I Shapiro, Khandan Keyomarsi
• Journal: American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting (Am Soc Clin Oncol Educ Book) Vol. 40 Pg. 115-126 (May 2020) ISSN: 1548-8756 [Electronic] United States
• PMID: 32421454 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Biological Products
• Biomarkers, Tumor
• Protein Kinase Inhibitors
• CDK4 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biological Products (pharmacology, therapeutic use)
• Biomarkers, Tumor
• Cell Cycle
• Cyclin-Dependent Kinase 4 (antagonists & inhibitors)
• Cyclin-Dependent Kinase 6 (antagonists & inhibitors)
• Drug Resistance, Neoplasm
• Humans
• Neoplasms (drug therapy)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)