Autor: Izabella Danezi Felin | Publicado: 2017-06-26T10:56:00-03:00

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<![endif]--> Grupo de monitores 2017/ 1 da disciplina de Patologia Geral Médica e do Projeto PATONLINE estuda, revisa e compartilha conhecimentos relativos aos avanços na área da Pato-Onco- Genética: 

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TERAPIA ALVO ANTI-RECEPTOR DE FATOR DE CRESCIMENTO
EPIDÉRMICO (ANTI-EGFR) E AQUISIÇÃO DE RESISTÊNCIA ADQUIRIDA NO CÂNCER DE PULMÃO
NÃO PEQUENAS CÉLULAS




O câncer de pulmão é
um dos mais incidentes e uma das principais causas de morte por câncer. O receptor do fator de crescimento epidérmico (EGFR) é
uma proteína de superfície celular, encontrada de forma hiperexpressa,
especialmente, no câncer de pulmão não pequenas células, determinando maior proliferação
tumoral, ativando sobrevivência e
invasão celular. O diagnóstico molecular de mutações em EGFR se tornou
necessário para a definição do tratamento adequado em pacientes com câncer de
pulmão, pois são potenciais alvos terapêuticos. Todos os pacientes com câncer
de pulmão não pequenas células (CPCNP), em estágio avançado, devem ser
submetidos à pesquisa de mutações genéticas em EGFR, pois os que tiverem mutações ativadoras em EGFR podem se
beneficiar &nbsp;da terapia alvo personalizada
com inibidores de tirosina quinase (TKI)
do EGFR (EGFR-TKIs), ou seja, terapia anti-EGFR. O CPNPC em geral tem
mutações de sensibilidade do EGFR em 15-20% dos casos e apresentam uma resposta
inicial intensa, porém com possível resistência ao tratamento após
aproximadamente um ano de terapia. Em cerca de 50-60% dos pacientes o motivo da
resistência adquirida é a mutação adicional denominada de T790M. Os TKI-
Gefitinibe e Erlotinibe - têm sido utilizados para o tratamento do CPNPC. Porém
novos TKI de terceira geração estão sendo
utilizados para superar a resistência ao tratamento dos CPNPC que tem mutação T790M+. A heterogeneidade
genética e as alterações genéticas que conferem resistência à terapia alvo são
fundamentais no desenvolvimento de resistência adquirida aos agentes anti-EGFR.
Além do desenvolvimento de mutações pontuais na região do ectodomínio de EGFR
(T790M), há mutações em genes integrantes da via de EGFR. Entretanto, a
presença destas alterações não explica todos os casos de resistência adquirida.
Outros mecanismos precisam ser caracterizados e pesquisados.