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Mecanismos de ação e ação terapêutica dos inibidores do proteossoma no mieloma múltiplo : artigo de revisão

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Detalhes bibliográficos
Resumo:Since the publication of the clinical and preclinical trials of bortezomib (BTZ), the first proteossome inhibitor (PI) approved for the treatment of relapsed/ refractory multiple myeloma (MM), there was a shift in the management of MM that has substantially improved survival in MM patients over the past decade. Their mechanism of action, through the reversible inhibition of 26S proteossome, results in disrupting multiple cellular signaling pathways involved in MM cell growth, proliferation and survival. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. BTZ is now an established component of induction therapy for either eligible or ineligible patients for autologous stem cell transplantation. Furthermore, a new route of bortezomib administration, subcutaneous infusion, has recently been approved. Recently, several new agents have been introduced into the clinic, including arfilzomib, marizomib, and MLN9708, and trials investigating these second generation PIs in patients with relapsed/ refractory MMs have demonstrated positive results.
Autores principais:Nogueira, Violeta da Cruz
Assunto:Via ubiquitina-proteossoma Inibidores do protessoma Bortezomib Mieloma múltiplo
Ano:2014
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:português
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Since the publication of the clinical and preclinical trials of bortezomib (BTZ), the first proteossome inhibitor (PI) approved for the treatment of relapsed/ refractory multiple myeloma (MM), there was a shift in the management of MM that has substantially improved survival in MM patients over the past decade. Their mechanism of action, through the reversible inhibition of 26S proteossome, results in disrupting multiple cellular signaling pathways involved in MM cell growth, proliferation and survival. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. BTZ is now an established component of induction therapy for either eligible or ineligible patients for autologous stem cell transplantation. Furthermore, a new route of bortezomib administration, subcutaneous infusion, has recently been approved. Recently, several new agents have been introduced into the clinic, including arfilzomib, marizomib, and MLN9708, and trials investigating these second generation PIs in patients with relapsed/ refractory MMs have demonstrated positive results.