title: Progress in BCL2 inhibition for patients with chronic lymphocytic leukemia.
abstract: The prosurvival protein BCL2 is uniformly expressed in chronic lymphocytic leukemia (CLL), and enables leukemia cell survival in the face of cytotoxic treatment and increasing genomic, metabolic, and oxidative stresses. The therapeutic potential of BCL2 inhibition was first observed in the clinic following BCL2 antisense therapy. Subsequently, a number of small molecule inhibitors were developed to mimic the function of the pro-apoptotic BH3-only proteins (BH3-mimetics). These molecules are now in late-phase clinical trials and demonstrate potent activity, including the occurrence of acute tumor lysis syndrome in subjects with multiply relapsed, chemorefractory CLL. In this review, we discuss the history and summarize current knowledge regarding BCL2 inhibition as therapy of CLL.
authors.affiliation: Haematology Department, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia. Electronic address: constantine.tam@petermac.org.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.affiliation: Haematology Department, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia; University of Melbourne, Parkville, Victoria, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: University of Melbourne, Parkville, Victoria, Australia; Department of Clinical Haematology and BMT, Royal Melbourne Hospital, Parkville, Victoria, Australia; Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: ABT-199; ABT-263; ABT-737; Apoptosis