title: The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy.
abstract: Tumour development requires a combination of defects that allow nascent neoplastic cells to become self-sufficient for cell proliferation and insensitive to signals that normally restrain cell growth. Among the latter, evasion of programmed cell death (apoptosis) has proven to be critical for the development and sustained growth of many, perhaps all, cancers. Apoptotic cell death is regulated by complex interactions between pro-survival members and two subgroups of pro-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family. In this invited review article, we reminisce on the discovery of Bcl-2, the first regulator of cell death identified, we discuss the mechanisms that control apoptotic cell death, focussing on how defects in this process promote the development and sustained growth of tumours and also affect their responses to anticancer therapeutics and, finally, we describe how current knowledge of the regulatory networks of apoptosis is exploited to develop novel approaches for cancer therapy.
authors.affiliation: Molecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3050, Australia.
authors.forename: P N
authors.initials: PN
authors.lastname: Kelly
authors.forename: A
authors.initials: A
authors.lastname: Strasser
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2