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
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.
