CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment DOI Creative Commons
Tong Gao, Ying Sun, Ping Leng

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 12, 2025

Dysregulated cell cycle progression is a well-established hallmark of cancer, driving the development targeted antitumor therapies that intervene at specific phases cycle. Among these therapeutic targets, cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as critical regulators progression, with their aberrant activation being strongly implicated in tumorigenesis cancer progression. Currently, multiple CDK4/6 inhibitors received clinical approval for hormone receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative breast demonstrating dual mechanisms through both arrest enhancement immunity. However, implementation faces two major challenges: inevitable acquired resistance during prolonged treatment, need optimized combination strategies other anticancer agents to achieve synergistic efficacy. This review systematically examines molecular underlying inhibitor function characterizes currently approved agents. Importantly, it synthesizes recent discoveries regarding mechanisms, including dysregulated checkpoints, compensatory signaling pathway activation, tumor microenvironment adaptations. Furthermore, we critically evaluate emerging approaches targeting mechanisms. By integrating mechanistic insights evidence, this analysis aims provide actionable overcoming maximizing potential management.

Language: Английский

CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment DOI Creative Commons
Tong Gao, Ying Sun, Ping Leng

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 12, 2025

Dysregulated cell cycle progression is a well-established hallmark of cancer, driving the development targeted antitumor therapies that intervene at specific phases cycle. Among these therapeutic targets, cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as critical regulators progression, with their aberrant activation being strongly implicated in tumorigenesis cancer progression. Currently, multiple CDK4/6 inhibitors received clinical approval for hormone receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative breast demonstrating dual mechanisms through both arrest enhancement immunity. However, implementation faces two major challenges: inevitable acquired resistance during prolonged treatment, need optimized combination strategies other anticancer agents to achieve synergistic efficacy. This review systematically examines molecular underlying inhibitor function characterizes currently approved agents. Importantly, it synthesizes recent discoveries regarding mechanisms, including dysregulated checkpoints, compensatory signaling pathway activation, tumor microenvironment adaptations. Furthermore, we critically evaluate emerging approaches targeting mechanisms. By integrating mechanistic insights evidence, this analysis aims provide actionable overcoming maximizing potential management.

Language: Английский

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