卵巢癌是妇科3大肿瘤之一,发病率逐年上升。尽管目前对卵巢癌的治疗方法已取得长足进步,但是患者生存率仍较低,寻求更加高效低不良反应的治疗方法仍是临床医师及科研人员不懈努力的方向。近年来已在卵巢癌中进行了多种聚腺苷二磷酸核糖...卵巢癌是妇科3大肿瘤之一,发病率逐年上升。尽管目前对卵巢癌的治疗方法已取得长足进步,但是患者生存率仍较低,寻求更加高效低不良反应的治疗方法仍是临床医师及科研人员不懈努力的方向。近年来已在卵巢癌中进行了多种聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂的临床研究。niraparib为新型PARP抑制剂,也是首个应用于复发型卵巢上皮癌的靶向药物,对乳腺癌易感基因(breast cancer susceptibility gene,BRCA)野生型及突变型患者均有较好的治疗效果,与放疗及化疗联合应用也有良好效果。本文对niraparib在卵巢癌中的应用进行综述。展开更多
PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies,particularly when the tumors are deficient in DNA repair p...PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies,particularly when the tumors are deficient in DNA repair pathways.However,as the case with other chemotherapeutic agents,their effectiveness is often compromised by the development of resistance.PARP inhibitors have consistently been reported to promote autophagy,a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins.Autophagy can exhibit different functional properties,the most prominent being cytoprotective.In addition,both cytotoxic and non-protective functions forms have also been identified.In this review,we explore the available literature regarding the different roles of autophagy in response to clinically-used PARP inhibitors,highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of PARP inhibition and to overcome the development of resistance.展开更多
Ovarian cancer is one of the most lethal gynecologic cancers.The standard therapy for ovarian cancer has been the same for the past two decades,a combination treatment of platinum with paclitaxel.Recently,the FDA appr...Ovarian cancer is one of the most lethal gynecologic cancers.The standard therapy for ovarian cancer has been the same for the past two decades,a combination treatment of platinum with paclitaxel.Recently,the FDA approved three new therapeutic drugs,two poly(ADP-ribose)polymerase inhibitors(olaparib and niraparib)and one vascular endothelial growth factor inhibitor(bevacizumab)as maintenance therapies for ovarian cancer.In this review,we summarize the resistance mechanisms for conventional platinum-based chemotherapy and for the newly FDA-approved drugs.展开更多
PolyADP ribose polymerase inhibitors(PARPi)have transformed the treatment of ovarian cancer.Particularly in high-grade serous ovarian cancer(HGSOC),a disease characterized by homologous recombination deficiency(HRD),P...PolyADP ribose polymerase inhibitors(PARPi)have transformed the treatment of ovarian cancer.Particularly in high-grade serous ovarian cancer(HGSOC),a disease characterized by homologous recombination deficiency(HRD),PARPi have had a rapid and profound impact on the disease course,as well as biologic and biomarker definitions of HGSOC,thereby creating a paradigm shift in the approach to treatment.In this review,we discuss the role of PARPi in the maintenance treatment of HGSOC,its effect on platinum sensitivity,and cross-resistance between platinum and PARP inhibitors.展开更多
文摘卵巢癌是妇科3大肿瘤之一,发病率逐年上升。尽管目前对卵巢癌的治疗方法已取得长足进步,但是患者生存率仍较低,寻求更加高效低不良反应的治疗方法仍是临床医师及科研人员不懈努力的方向。近年来已在卵巢癌中进行了多种聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂的临床研究。niraparib为新型PARP抑制剂,也是首个应用于复发型卵巢上皮癌的靶向药物,对乳腺癌易感基因(breast cancer susceptibility gene,BRCA)野生型及突变型患者均有较好的治疗效果,与放疗及化疗联合应用也有良好效果。本文对niraparib在卵巢癌中的应用进行综述。
基金Research in Dr.Gewirtz’s laboratory is supported by Grants#CA268819 and CA239706 from the National Cancer InstituteNational Institutes of Health and Grant#W81XWH 19-1-0490 from the Department of Defense Congressionally Directed Breast Cancer Research Program.
文摘PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies,particularly when the tumors are deficient in DNA repair pathways.However,as the case with other chemotherapeutic agents,their effectiveness is often compromised by the development of resistance.PARP inhibitors have consistently been reported to promote autophagy,a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins.Autophagy can exhibit different functional properties,the most prominent being cytoprotective.In addition,both cytotoxic and non-protective functions forms have also been identified.In this review,we explore the available literature regarding the different roles of autophagy in response to clinically-used PARP inhibitors,highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of PARP inhibition and to overcome the development of resistance.
文摘Ovarian cancer is one of the most lethal gynecologic cancers.The standard therapy for ovarian cancer has been the same for the past two decades,a combination treatment of platinum with paclitaxel.Recently,the FDA approved three new therapeutic drugs,two poly(ADP-ribose)polymerase inhibitors(olaparib and niraparib)and one vascular endothelial growth factor inhibitor(bevacizumab)as maintenance therapies for ovarian cancer.In this review,we summarize the resistance mechanisms for conventional platinum-based chemotherapy and for the newly FDA-approved drugs.
文摘PolyADP ribose polymerase inhibitors(PARPi)have transformed the treatment of ovarian cancer.Particularly in high-grade serous ovarian cancer(HGSOC),a disease characterized by homologous recombination deficiency(HRD),PARPi have had a rapid and profound impact on the disease course,as well as biologic and biomarker definitions of HGSOC,thereby creating a paradigm shift in the approach to treatment.In this review,we discuss the role of PARPi in the maintenance treatment of HGSOC,its effect on platinum sensitivity,and cross-resistance between platinum and PARP inhibitors.
