Potential of BCL2 as a target for chronic lymphocytic leukemia treatment.
Expert Rev Hematol
; 11(5): 391-402, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29561706
ABSTRACT
INTRODUCTION:
Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies. Among these new drugs, venetoclax, an orally bioavailable BCL2 inhibitor, has shown high efficacy also in relapsed/refractory CLL with TP53 disruption. Venetoclax has also been tested in combination with other drugs without compromising venetoclax dose and with a good safety profile. Areas covered This article covers the biology of apoptosis in CLL from a translational viewpoint and deals with the mode of action of BCL2 inhibitors, in particular venetoclax. On this biological rationale, the review then focuses on the results obtained in clinical trials with venetoclax in CLL. Expert commentary The availability of venetoclax represents a major advance in CLL treatment and offers new opportunities to further improve the results obtained until now by combining venetoclax with other agents. Venetoclax has achieved responses also in patients with TP53 disruption. These results strongly suggest that the mechanism by which venetoclax kills CLL cells might overcome a dysfunctional TP53 that is a major hallmark of chemorefractoriness to conventional antineoplastic agents.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Leucemia Linfocítica Crônica de Células B
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Apoptose
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Resistencia a Medicamentos Antineoplásicos
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Compostos Bicíclicos Heterocíclicos com Pontes
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Proteínas Proto-Oncogênicas c-bcl-2
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Expert Rev Hematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália