多聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂显著改善了携带乳腺癌易感基因(breast cancer susceptibility gene,BRCA)突变的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)...多聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂显著改善了携带乳腺癌易感基因(breast cancer susceptibility gene,BRCA)突变的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者的生存结局。美国食品药品监督管理局(Foodand Drug Administration,FDA)已批准奥拉帕利和卢卡帕利用于治疗mCRPC患者,而奥拉帕利是目前唯一获得国家药品监督管理局(National Medical Products Administration,NMPA)批准用于前列腺癌治疗的PARP抑制剂。目前我国尚无PARF抑制剂在前列腺癌中应用的不良反应预防及管理共识。因此,中国医师协会泌尿外科医师分会共识专家组制定了《PARP抑制剂治疗前列腺癌不良反应预防及管理中国专家共识》,本共识基于国际最新临床研究、临床实践以及FDA和NMPA的批准情况,旨在总结PARP抑制剂治疗mCRPC的血液学和非血液学不良反应并制定相关的管理策略,为临床用药及不良反应管理提供参考。展开更多
Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-a...Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-analysis to compare these first-line regimens and to determine the regimen with the best efficacy.Methods:A systematic search of PubMed,EMBASE,the Cochrane Central Register of Controlled Bases,and mi-nutes of major conferences was performed.Progression-free survival(PFS),overall survival(OS),and objective response rate(ORR)were analyzed via network meta-analysis using the R software(R Core Team,Vienna,Austria).The efficacy of the treatment regimens was compared using hazard ratios and 95%confidence intervals.Results:A total of 29 randomized controlled trials involving 4607 patients were analyzed.The ranking was based on the surface under the cumulative ranking curve.Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR.For programmed death-ligand 1(PD-L1)and breast cancer susceptibility gene(BRCA)mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib was superior to docetaxel plus capecitabine.No significant difference was observed among the treatments in Os.Neutropenia,diarrhea,and fatigue were common serious adverse events.Conclusion:Cisplatin combined with nab-paclitaxel or paclitaxel is the preferred first-line treatment for mTNBC.For PD-L1 and BRCA mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option,Neutropenia,diarrhea,and fatigue are frequently occurring serious adverseevents.展开更多
Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway c...Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.展开更多
文摘多聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂显著改善了携带乳腺癌易感基因(breast cancer susceptibility gene,BRCA)突变的转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者的生存结局。美国食品药品监督管理局(Foodand Drug Administration,FDA)已批准奥拉帕利和卢卡帕利用于治疗mCRPC患者,而奥拉帕利是目前唯一获得国家药品监督管理局(National Medical Products Administration,NMPA)批准用于前列腺癌治疗的PARP抑制剂。目前我国尚无PARF抑制剂在前列腺癌中应用的不良反应预防及管理共识。因此,中国医师协会泌尿外科医师分会共识专家组制定了《PARP抑制剂治疗前列腺癌不良反应预防及管理中国专家共识》,本共识基于国际最新临床研究、临床实践以及FDA和NMPA的批准情况,旨在总结PARP抑制剂治疗mCRPC的血液学和非血液学不良反应并制定相关的管理策略,为临床用药及不良反应管理提供参考。
文摘Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-analysis to compare these first-line regimens and to determine the regimen with the best efficacy.Methods:A systematic search of PubMed,EMBASE,the Cochrane Central Register of Controlled Bases,and mi-nutes of major conferences was performed.Progression-free survival(PFS),overall survival(OS),and objective response rate(ORR)were analyzed via network meta-analysis using the R software(R Core Team,Vienna,Austria).The efficacy of the treatment regimens was compared using hazard ratios and 95%confidence intervals.Results:A total of 29 randomized controlled trials involving 4607 patients were analyzed.The ranking was based on the surface under the cumulative ranking curve.Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR.For programmed death-ligand 1(PD-L1)and breast cancer susceptibility gene(BRCA)mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib was superior to docetaxel plus capecitabine.No significant difference was observed among the treatments in Os.Neutropenia,diarrhea,and fatigue were common serious adverse events.Conclusion:Cisplatin combined with nab-paclitaxel or paclitaxel is the preferred first-line treatment for mTNBC.For PD-L1 and BRCA mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option,Neutropenia,diarrhea,and fatigue are frequently occurring serious adverseevents.
文摘Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.
