Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion pro...Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.展开更多
YangAbstractThe use of the BCL2 inhibitor venetoclax has transformed the management of patients with acute myeloid leukemia(AML)who are ineligible for intensive chemotherapy.By triggering intrinsic apoptosis,the drug ...YangAbstractThe use of the BCL2 inhibitor venetoclax has transformed the management of patients with acute myeloid leukemia(AML)who are ineligible for intensive chemotherapy.By triggering intrinsic apoptosis,the drug is an excellent illustration of how our greater understanding of molecular cell death pathways can be translated into the clinic.Nevertheless,most venetoclax-treated patients will relapse,suggesting the need to target additional regulated cell death pathways.To highlight advances in this strategy,we review the recognized regulated cell death pathways,including apoptosis,necroptosis,ferroptosis and autophagy.Next,we detail the therapeutic opportunities to trigger regulated cell death in AML.Finally,we describe the main drug discovery challenges for regulated cell death inducers and their translation into clinical trials.A better knowledge of the molecular pathways regulating cell death represents a promising strategy to develop new drugs to cure resistant or refractory AML patients,particularly those resistant to intrinsic apoptosis.展开更多
基金supported by grants from National Science Foundation of China (No. 31071258)The Ministry of Science and Technology of China (Pre-973 Plan: No. 2011CB512101+1 种基金 863 Plan: No. 2011AA020114)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.
基金supported by the National Cancer Institute(R37CA218259,TWM).
文摘YangAbstractThe use of the BCL2 inhibitor venetoclax has transformed the management of patients with acute myeloid leukemia(AML)who are ineligible for intensive chemotherapy.By triggering intrinsic apoptosis,the drug is an excellent illustration of how our greater understanding of molecular cell death pathways can be translated into the clinic.Nevertheless,most venetoclax-treated patients will relapse,suggesting the need to target additional regulated cell death pathways.To highlight advances in this strategy,we review the recognized regulated cell death pathways,including apoptosis,necroptosis,ferroptosis and autophagy.Next,we detail the therapeutic opportunities to trigger regulated cell death in AML.Finally,we describe the main drug discovery challenges for regulated cell death inducers and their translation into clinical trials.A better knowledge of the molecular pathways regulating cell death represents a promising strategy to develop new drugs to cure resistant or refractory AML patients,particularly those resistant to intrinsic apoptosis.
基金supported by grants from the National Natural Science Foundation of China(90919044 and 81170518)High and New Technology Pro-gram of PLA(2010gxjs091)Capital Medical Development Scientific Research Fund(No.2007-2040)
