Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) play a crucial role in cancer treatment, particularly in breast cancer, and their mechanism of drug resistance is a topic of global interest in research. Hence, it is vital to comprehend the distinctions between various CDK4/6i, including their mechanisms of action and resistance mechanisms. This article aims to summarize the metabolic and transport variations as well as the differences in resistance among the three FDA-approved CDK4/6 inhibitors: Abemaciclib, Palbociclib, and Ribociclib. It also aims to discuss how these differences impact the effectiveness and safety of anticancer drugs. It was conducted in March 2023 to search PubMed, Embase, and Web of Science for literature related to this topic. Despite all being CDK4/6i, differences in their metabolism and transport were found, which are related to their chemical structure. Moreover, there are variations in preclinical pharmacology, pharmacokinetics, and clinical safety and efficacy of the different inhibitors. Genetic mutations, drug tolerance, and other factors may influence CDK4/6 resistance mechanisms. Currently, the resistance mechanisms differences of the three drugs remain largely unknown, and there are differences in the resistance mechanisms among them, necessitating further exploration and research.

Automated summary

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are crucial in cancer treatment, especially breast cancer, and understanding their differences in mechanism of action and resistance is vital. This study aimed to summarize the metabolic and transport variations as well as resistance differences among the FDA-approved CDK4/6 inhibitors: Abemaciclib, Palbociclib, and Ribociclib. Variations in metabolism, preclinical pharmacology, pharmacokinetics, safety, and efficacy were found among the inhibitors. Genetic mutations and drug tolerance may influence CDK4/6 resistance mechanisms. Further exploration and research are needed due to the remaining unknowns and differences in resistance mechanisms among the three drugs.