skip to main content
Idioma:

Computer simulations of the signalling network in FLT3 + -acute myeloid leukaemia - indications for an optimal dosage of inhibitors against FLT3 and CDK6

Buetti-Dinh, Antoine ; Friedman, Ran

BMC bioinformatics, 2018-04, Vol.19 (1), p.155-155, Article 155 [Periódico revisado por pares]

England: BioMed Central Ltd

Texto completo disponível

Citações Citado por
  • Título:
    Computer simulations of the signalling network in FLT3 + -acute myeloid leukaemia - indications for an optimal dosage of inhibitors against FLT3 and CDK6
  • Autor: Buetti-Dinh, Antoine ; Friedman, Ran
  • Assuntos: Acute myelocytic leukemia ; Acute myeloid leukaemia ; Analysis ; Biomedical Sciences ; Biomedicinsk vetenskap ; Care and treatment ; Combination therapy ; Computer simulation ; Development and progression ; Drug resistance ; Gene mutation ; Genetic aspects ; Knowledge-based analysis
  • É parte de: BMC bioinformatics, 2018-04, Vol.19 (1), p.155-155, Article 155
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies. Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone. The PI3K pathway provided a basis for resistance to treatments. Alternative signalling pathways could not, however, restore cancer growth signals (proliferation and loss of apoptosis) to the same levels as prior to treatment, which may explain why FLT3 resistance mutations are the most common resistance mechanism. Finally, sensitivity analysis suggested the existence of optimal doses of FLT3 and CDK6 inhibitors in terms of efficacy and toxicity.
  • Editor: England: BioMed Central Ltd
  • Idioma: Inglês
Links
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.