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BCL-2 as a therapeutic target in chronic lymphocytic leukemia.

Abstract Venetoclax (formerly ABT-199) was recently approved in the United States for the treatment of patients who have relapsed or refractory chronic lymphocytic leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of CLL. The potency of venetoclax has been associated with a unique ability to induce deep (minimal residual disease-negative) complete remissions that appear to be durable. Its toxicity profile includes manageable hematologic toxicities, as well as the potential for tumor lysis syndrome. Here, we review the BCL-2 pathway and the mechanism of action of BCL-2 inhibitors, the activity and safety profile of venetoclax, and the practical application of venetoclax in the management of patients with CLL.
PMID
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Authors

Mayor MeshTerms

Molecular Targeted Therapy

Keywords
Journal Title clinical advances in hematology & oncology : h&o
Publication Year Start




PMID- 28398276
OWN - NLM
STAT- MEDLINE
DA  - 20170411
DCOM- 20170420
LR  - 20170420
IS  - 1543-0790 (Print)
IS  - 1543-0790 (Linking)
VI  - 15
IP  - 3
DP  - 2017 Mar
TI  - BCL-2 as a therapeutic target in chronic lymphocytic leukemia.
PG  - 210-218
AB  - Venetoclax (formerly ABT-199) was recently approved in the United States for the 
      treatment of patients who have relapsed or refractory chronic lymphocytic
      leukemia (CLL) with the 17p deletion. Venetoclax has demonstrated marked activity
      as monotherapy as well as in combination with cytotoxic chemotherapies, B-cell
      receptor inhibitors, and anti-CD20 monoclonal antibodies across the spectrum of
      CLL. The potency of venetoclax has been associated with a unique ability to
      induce deep (minimal residual disease-negative) complete remissions that appear
      to be durable. Its toxicity profile includes manageable hematologic toxicities,
      as well as the potential for tumor lysis syndrome. Here, we review the BCL-2
      pathway and the mechanism of action of BCL-2 inhibitors, the activity and safety 
      profile of venetoclax, and the practical application of venetoclax in the
      management of patients with CLL.
FAU - Daniel, Catherine
AU  - Daniel C
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
FAU - Mato, Anthony R
AU  - Mato AR
AD  - Center for Chronic Lymphocytic Leukemia, Abramson Cancer Center, University of
      Pennsylvania, Philadelphia, Pennsylvania.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Adv Hematol Oncol
JT  - Clinical advances in hematology & oncology : H&O
JID - 101167661
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Antigen, B-Cell)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Combined Modality Therapy
MH  - Disease Management
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/*metabolism/mortality
MH  - *Molecular Targeted Therapy
MH  - Neutropenia/diagnosis/drug therapy/etiology
MH  - Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors/metabolism
MH  - Receptors, Antigen, B-Cell/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Treatment Outcome
MH  - Tumor Lysis Syndrome/diagnosis/etiology/therapy
EDAT- 2017/04/12 06:00
MHDA- 2017/04/21 06:00
CRDT- 2017/04/12 06:00
PST - ppublish
SO  - Clin Adv Hematol Oncol. 2017 Mar;15(3):210-218.

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