Inhibitor of apoptosis proteins in hematological malignancies.
Apoptosis or programmed cell death is a key mechanism to control tissue homeostasis, for example, in the hematopoietic system. Thus, resistance to apoptosis can contribute to the development of leukemia or lymphoma. Inhibitors of apoptosis (IAP) proteins block cell death pathways at a central node by interfering with the activation of effector caspases. As increased expression levels of IAPs are found in hematological malignancies and have been correlated with poor prognosis, IAPs could be exploited as therapeutic targets and prognostic markers. Various strategies have been developed to target IAPs for therapeutic purposes in leukemia and lymphoma cells, including small-molecule inhibitors and antisense oligonucleotides. These agents could directly induce apoptosis in malignant cells or sensitize these cells to other cytotoxic agents. Thus, IAPs present promising targets for the development of new biomarkers and cancer therapeutics in hematological malignancies.
Fulda
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University Children's Hospital, Ulm University, Ulm, Germany. simone.fulda@uniklinik-ulm.de
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000502:physiology; D002648:Child; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000502:physiology; D016503:Drug Delivery Systems; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D053218:Receptors, Death Domain / Q000502:physiology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D053218:Receptors, Death Domain; D020169:Caspases