Growth control of normal and malignant lymphocytes--cell death research from basic concepts to signal pathways and translation into the clinic.
Twenty years ago the fist bona fide death receptor, APO-1/FAS/CD95 was discovered along with the pathways that regulate programmed cell death or apoptosis. From the very beginning, this research was considered to have substantial impact on diseases and to provide a rational strategy for therapeutic intervention. In particular cell death research proved to be the key for the development of novel strategies for cancer therapy. In the past two decades, deregulated apoptosis in tumors has been delineated and possible targets for therapeutic intervention have been identified. However, it still took a long way until this work could be translated into clinical trials only in the past few years. Current strategies involve modification of apoptosis signalling based on our knowledge of sensitivity and resistance for apoptosis induction rather than the use of individual agents for cytotoxicity. In this review, an overview of the developments in the field from basic discoveries to the recent clinical trials is given.
Debatin
K-M
KM
Universitätsklinik für Kinder- und Jugendmedizin, Klinikbereich Michelsberg, Kinderonkologisches Zentrum, Ulm, Germany. klaus-michael.debatin@uniklinik-ulm.de
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D017173:Caenorhabditis elegans; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics*; D002648:Child; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D053218:Receptors, Death Domain / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor