title: Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia.
abstract: Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy. g.delpoeta@tin.it.
authors.forename: G
authors.initials: G
authors.lastname: Del Poeta
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Postorino
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pupo
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: M I
authors.initials: MI
authors.lastname: Del Principe
authors.affiliation: Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dal Bo
authors.affiliation: Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
authors.forename: T
authors.initials: T
authors.lastname: Bittolo
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Buccisano
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Mariotti
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Iannella
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Maurillo
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Venditti
authors.affiliation: Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.
authors.forename: V
authors.initials: V
authors.lastname: Gattei
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: de Fabritiis
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cantonetti
authors.affiliation: Hematology, Dipartimento di Biomedicina e Prevenzione, Universit à degli Studi di Roma Tor Vergata, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; C579720:venetoclax
keywords: 17p deletion/TP53 mutation; ABT-199; Bcl-2; Chronic lymphocytic leukemia; Novel tyrosine kinase inhibitors; Venetoclax