CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase ...CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.展开更多
Organic transistors,as a new generation of electronic technology,play a crucial role in the development of low-cost and flexible electronic applications,garnering extensive research interest.Two-dimensional organic se...Organic transistors,as a new generation of electronic technology,play a crucial role in the development of low-cost and flexible electronic applications,garnering extensive research interest.Two-dimensional organic semiconductors(2D-OSCs)with molecular layer thickness have shown important value in exploring the charge transfer mechanism of molecules,building high-performance transistor devices and large-scale flexible integrated circuits due to their advantages,such as long-range order of molecular arrangement,no grain boundaries,few impurities and defects,and high charge transfer efficiency.Currently,researchers are actively engaged in enhancing the performance of 2D organic field-effect transistors(2D-OFETs),which includes the design of high-performance molecular structures,controlled growth of large-area,high-quality crystals,and fabrication process.Therefore,this article focuses on the comprehensive performance optimization of 2D-OFETs,reviewing the relationship between key performance parameters and device structure,the latest research progress,and the main challenges currently faced.Furthermore,we delve into and summarize the optimization mechanisms and corresponding strategies for 2D-OFET mobility,dielectric layer performance,power consumption,and contact resistance.Lastly,we provide an outlook on the manufacturing technology of 2D-OFETs and their application prospects,aiming to guide future research and development.Ongoing research and development efforts in this area have the potential to make significant advances.展开更多
基金sponsored by the Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.
文摘CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.
基金support from the National Key R&D Program of China(Nos.2024YFB4405300 and 2024YFB4405203)the Natural Science Foundation of Jiangsu Province(No.BK20220397)+6 种基金the National Natural Science Foundation of China(Nos.62204130,62474094,and T2322014)NSFC-DFG“Mobility”project(No.M0604)Guangdong Province Research and Development in Key Fields from Guangdong Greater Bay Area Institute of Integrated Circuit and System(No.2021B0101280002)Guangzhou City Research and Development Program in Key Field(No.20210302001)in part by Guangdong Key Laboratory of Integrated Circuit Technology and Products Based on Fully Depleted Silicon On Insulator,the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.22KJB510010)Guangdong Provincial Key Laboratory of Integrated Circuit Technology and Products Based on Fully Depleted Silicon On Insulator(2024)(No.2024B1212020005)Guangdong Province Pearl-River Talent Program(No.2023JC11X250).
文摘Organic transistors,as a new generation of electronic technology,play a crucial role in the development of low-cost and flexible electronic applications,garnering extensive research interest.Two-dimensional organic semiconductors(2D-OSCs)with molecular layer thickness have shown important value in exploring the charge transfer mechanism of molecules,building high-performance transistor devices and large-scale flexible integrated circuits due to their advantages,such as long-range order of molecular arrangement,no grain boundaries,few impurities and defects,and high charge transfer efficiency.Currently,researchers are actively engaged in enhancing the performance of 2D organic field-effect transistors(2D-OFETs),which includes the design of high-performance molecular structures,controlled growth of large-area,high-quality crystals,and fabrication process.Therefore,this article focuses on the comprehensive performance optimization of 2D-OFETs,reviewing the relationship between key performance parameters and device structure,the latest research progress,and the main challenges currently faced.Furthermore,we delve into and summarize the optimization mechanisms and corresponding strategies for 2D-OFET mobility,dielectric layer performance,power consumption,and contact resistance.Lastly,we provide an outlook on the manufacturing technology of 2D-OFETs and their application prospects,aiming to guide future research and development.Ongoing research and development efforts in this area have the potential to make significant advances.
