Targeted therapy with a selective BCL-2 inhibitor in older patients with acute myeloid leukemia
Hematol., Transfus. Cell Ther. (Impr.)
;
41(2): 169-177, Apr.-June 2019. tab, graf
Artigo
em Inglês
| LILACS
| ID: biblio-1012177
ABSTRACT
ABSTRACT Background:
Older patients with acute myeloid leukemia are particularly difficult to treat, as they have a high risk of comorbidities, poor performance status and less tolerability to chemotherapy, as well as a more aggressive disease biology, responsible for the resistance to treatment. There is a need to explore novel therapeutic agents that are more effective and tolerable. Venetoclax, a BCL-2 inhibitor is a promising agent, as BCL-2 overexpression is present in 84% of acute myeloid leukemia patients at diagnosis and 95% of patients at relapse and has been associated with leukemia cell survival, chemotherapy resistance and poor prognosis.Objective:
To review the available data about venetoclax in acute myeloid leukemia and how it can influence the treatment in older patients.Methods:
Using the Pubmed database, we selected 29 articles published within the last 15 years, considering preclinical and clinical trials and review studies that combined venetoclax with acute myeloid leukemia.Results:
Venetoclax has demonstrated promising results in preclinical and clinical trials, especially in patients with poor prognosis and the IDH mutation, with an excellent side-effect profile. However, resistance seems to develop rapidly with venetoclax monotherapy, because of antiapoptotic escape mechanisms.Conclusions:
While the results with the use of venetoclax seem encouraging, it is not likely that targeting a single pathway will result in long-term disease control. The solution includes the use of combined therapy to block resistance mechanisms and enhance apoptosis, by reducing MCL-1, increasing BIM or inhibiting the complex IV in the mitochondria.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Leucemia Mieloide Aguda
/
Genes bcl-2
/
Proteína Agonista de Morte Celular de Domínio Interatuante com BH3
/
Terapia de Alvo Molecular
Idioma:
Inglês
Revista:
Hematol., Transfus. Cell Ther. (Impr.)
Assunto da revista:
Hematologia
/
TransfusÆo de Sangue
Ano de publicação:
2019
Tipo de documento:
Artigo
País de afiliação:
Portugal
Instituição/País de afiliação:
Hospital de São João/PT
/
Universidade do Porto/PT
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