目的总结CDK4/6抑制剂治疗乳腺癌所致不良反应的相关护理证据,为临床实践提供循证依据。方法采用PIPOST问题开发工具构建循证问题,按照“6S”证据金字塔模型,遵循自上而下的原则,系统检索BMJ Best Practice、Up To Date、澳大利亚乔安...目的总结CDK4/6抑制剂治疗乳腺癌所致不良反应的相关护理证据,为临床实践提供循证依据。方法采用PIPOST问题开发工具构建循证问题,按照“6S”证据金字塔模型,遵循自上而下的原则,系统检索BMJ Best Practice、Up To Date、澳大利亚乔安娜布里格斯研究所循证卫生保健数据库、美国国立指南数据库、美国国立综合癌症网络、加拿大医学会临床实践指南网、苏格兰校际指南网、国际指南协作网、英国国家卫生与临床优化研究所、新西兰指南协作组网站、加拿大安大护理学会、Pub Med、Web of Science、Cochrane Library、Embase、中国期刊全文数据库、万方学术期刊全文数据库、医脉通等,检索时限为建库起至2023年12月31日。由2~4名研究者进行文献筛选、质量评价、证据提取及整合。结果最终纳入17篇文献,其中包含1篇临床决策、1篇指南、2篇专家共识、4篇meta分析、1篇随机对照试验、2篇系统评价、6篇原始研究。从用药前评估、用药观察、皮肤护理、胃肠道反应管理、多学科协作管理、心理干预6个方面总结出17条证据。结论本研究总结了CDK4/6抑制剂治疗乳腺癌所致不良反应的相关护理证据,可为临床护理实践提供参考,护理人员可结合患者的临床症状与实际需求,实施规范化、个体化的护理干预。展开更多
Molecular glues(MGs), a class of small-molecule degraders, exhibit drug-like properties that generally conform to Lipinski's rule of five, while uniquely mediating the stabilization or induction of protein-protein...Molecular glues(MGs), a class of small-molecule degraders, exhibit drug-like properties that generally conform to Lipinski's rule of five, while uniquely mediating the stabilization or induction of protein-protein interactions. By altering the surface properties of either target proteins or E3 ligases, MGs promote the formation of a ternary complex comprising the MG, an E3 ligase, and a target protein. This interaction facilitates the polyubiquitination and subsequent degradation of the target protein via the ubiquitin-proteasome system.Owing to its distinctive mechanism of action and broad therapeutic potential, MG is offering novel approaches to disease treatment. This review summarizes recent advances in MGs targeting NEK7, WEE1, CDK2, GSPT1 and VAV1, emphasizing the rational design, benefits,and potential limitations, highlighting rational design principles, advantages, and current limitations including challenges in achieving selectivity and rational design that provide critical insights for enhancing MG efficacy. These developments are crucial for advancing the application and optimization of molecular glues targeting NEK7, WEE1, CDK2, GSPT1and VAV1.展开更多
Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-de...Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors that have become an innovative family of targeted therapy for hormone receptor-positive,Human Epidermal Growth factor receptor 2(HR+/HER2-)breast cancer.These inhibitors work by preventing the action of CDK4/6,which are crucial in the regulation of the cell cycle.Leading cancer cells to cell cycle arrest and undergo apoptosis.When these inhibitors are used with endocrine medicines like letrozole and fulvestrant,clinical trials lead positive impact in progression-free survival and,in a few cases,complete survival.However,despite their effectiveness,resistance mechanisms are primary and current acquired problems,requiring combined approaches with additional targeted medicines and continuous investigation into innovative therapeutic plans.To maintain patient compliance and quality of life,common side effects such as tiredness,gastrointestinal problems,and neutropenia need to be effectively managed.There is hopefulness for wider oncological applications as next-generation CDK inhibitor development and adaptive clinical trials continue to test their potential beyond breast cancer.CDK4/6 inhibitors continue to be a key part of breast cancer treatment as cancer biology advances,marking a major advancement towards more potent and customized cancer medicines.This review aims to provide current evidence on CDK4/6 inhibitors in HR+/HER2-breast cancer,highlighting their mechanisms,interaction with endocrine resistance,combination strategies,and emerging biomarkers guiding personalized therapy.展开更多
The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not...The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not been approved.A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market.Subsequently,resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment.In this review,we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors.Moreover,we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors,which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.展开更多
文摘目的总结CDK4/6抑制剂治疗乳腺癌所致不良反应的相关护理证据,为临床实践提供循证依据。方法采用PIPOST问题开发工具构建循证问题,按照“6S”证据金字塔模型,遵循自上而下的原则,系统检索BMJ Best Practice、Up To Date、澳大利亚乔安娜布里格斯研究所循证卫生保健数据库、美国国立指南数据库、美国国立综合癌症网络、加拿大医学会临床实践指南网、苏格兰校际指南网、国际指南协作网、英国国家卫生与临床优化研究所、新西兰指南协作组网站、加拿大安大护理学会、Pub Med、Web of Science、Cochrane Library、Embase、中国期刊全文数据库、万方学术期刊全文数据库、医脉通等,检索时限为建库起至2023年12月31日。由2~4名研究者进行文献筛选、质量评价、证据提取及整合。结果最终纳入17篇文献,其中包含1篇临床决策、1篇指南、2篇专家共识、4篇meta分析、1篇随机对照试验、2篇系统评价、6篇原始研究。从用药前评估、用药观察、皮肤护理、胃肠道反应管理、多学科协作管理、心理干预6个方面总结出17条证据。结论本研究总结了CDK4/6抑制剂治疗乳腺癌所致不良反应的相关护理证据,可为临床护理实践提供参考,护理人员可结合患者的临床症状与实际需求,实施规范化、个体化的护理干预。
基金supported by the National Natural Science Foundation of China (No. 82304306)the Hubei Key Laboratory of Kidney Disease Occurrence and Intervention Development Fund (No. 2023SB108)+4 种基金the Huangshi City Science and Innovation Team Project of China (CXPT2023000002)the talent introduction program from Hubei Polytechnic University (No.19XJK07R)the Department of Education of Hubei Provincial Science and Technology Research Project (No. D20234502)the PostDoctoral Research Start-up Fund of Lishui People's Hospital, Zhejiang, China (2023bsh002)the Zhejiang Provincial Postdoctoral Research Project of Meritorious Support (ZJ2024007)。
文摘Molecular glues(MGs), a class of small-molecule degraders, exhibit drug-like properties that generally conform to Lipinski's rule of five, while uniquely mediating the stabilization or induction of protein-protein interactions. By altering the surface properties of either target proteins or E3 ligases, MGs promote the formation of a ternary complex comprising the MG, an E3 ligase, and a target protein. This interaction facilitates the polyubiquitination and subsequent degradation of the target protein via the ubiquitin-proteasome system.Owing to its distinctive mechanism of action and broad therapeutic potential, MG is offering novel approaches to disease treatment. This review summarizes recent advances in MGs targeting NEK7, WEE1, CDK2, GSPT1 and VAV1, emphasizing the rational design, benefits,and potential limitations, highlighting rational design principles, advantages, and current limitations including challenges in achieving selectivity and rational design that provide critical insights for enhancing MG efficacy. These developments are crucial for advancing the application and optimization of molecular glues targeting NEK7, WEE1, CDK2, GSPT1and VAV1.
基金funded by School of Medical Sciences and Universiti Sains Malaysia。
文摘Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors that have become an innovative family of targeted therapy for hormone receptor-positive,Human Epidermal Growth factor receptor 2(HR+/HER2-)breast cancer.These inhibitors work by preventing the action of CDK4/6,which are crucial in the regulation of the cell cycle.Leading cancer cells to cell cycle arrest and undergo apoptosis.When these inhibitors are used with endocrine medicines like letrozole and fulvestrant,clinical trials lead positive impact in progression-free survival and,in a few cases,complete survival.However,despite their effectiveness,resistance mechanisms are primary and current acquired problems,requiring combined approaches with additional targeted medicines and continuous investigation into innovative therapeutic plans.To maintain patient compliance and quality of life,common side effects such as tiredness,gastrointestinal problems,and neutropenia need to be effectively managed.There is hopefulness for wider oncological applications as next-generation CDK inhibitor development and adaptive clinical trials continue to test their potential beyond breast cancer.CDK4/6 inhibitors continue to be a key part of breast cancer treatment as cancer biology advances,marking a major advancement towards more potent and customized cancer medicines.This review aims to provide current evidence on CDK4/6 inhibitors in HR+/HER2-breast cancer,highlighting their mechanisms,interaction with endocrine resistance,combination strategies,and emerging biomarkers guiding personalized therapy.
基金supported by the National Key R&D Program of China(No.2023YFC2706303)the National Natural Science Foundation of China(Nos.82373738 and 82304293)Natural Science Foundation of Jiangsu Province(Nos.SBK2024090146 and BK20221040).
文摘The inhibition of cyclin-dependent kinases(CDKs)is considered a promising strategy for cancer treatment due to their role in cell cycle regulation.However,CDK inhibitors with no selectivity among CDK families have not been approved.A CDK inhibitor with high selectivity for CDK4/6 exhibited significant treatment effects on breast cancer and has become a heavy bomb on the market.Subsequently,resistance gradually decreased the efficacy of selective CDK4/6 inhibitors in breast cancer treatment.In this review,we first introduce the development of selective CDK4/6 inhibitors and then explain the role of CDK2 activation in inducing resistance to CDK4/6 inhibitors.Moreover,we focused on the development of CDK2/4/6 inhibitors and selective CDK2 inhibitors,which will aid in the discovery of novel CDK inhibitors targeting the cell cycle in the future.
