RESUMO
El glioblastoma es un tumor cerebral primario muy agresivo y resistente al tratamiento convencional con quimio y radioterapia. Dado que el receptor del factor de crecimiento epidérmico (EGFR) se encuentra alterado en el 50% de los glioblastomas, representa actualmente una de las dianas terapéuticas más prometedoras en este tipo de tumores. Sin embargo, los inhibidores de la actividad cinasa del EGFR han generado escasos resultados en ensayos clínicos con pacientes con glioblastoma. En esta revisión se analiza la función del EGFR en el glioblastoma y se describen las aproximaciones terapéuticas dirigidas frente a dicho receptor en este tipo de tumores. Este tipo de análisis podría constituir un punto de partida para mejorar el diseño de futuras terapias para los glioblastomas, basadas en la inhibición de la función del EGFR (AU)
A glioblastoma is a primary brain tumour that is very aggressive and resistant to conventional treatment with chemo- or radiotherapy. Given that epidermic growth factor receptor (EGFR) is altered in 50% of glioblastomas, it is currently one of the most promising therapeutic targets in this kind of tumour. Yet, inhibitors of the kinase activity of EGFR have yielded poor results in clinical trials with patients with glioblastomas. In this review we analyse the function of EGFR in glioblastomas and outline the therapeutic approaches aimed against this receptor in this kind of tumour. This sort of analysis could be a starting point for improving the design of future therapies for glioblastomas, based on inhibiting the EGFR function (AU)
Assuntos
Feminino , Humanos , Masculino , Genes erbB-1/genética , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Glioblastoma/complicações , Glioblastoma/metabolismo , Carcinogênese/genética , Mitose/genética , Ensaios Clínicos como Assunto/instrumentação , Ensaios Clínicos como Assunto/métodos , Tomografia/métodos , Genes erbB-1/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Glioblastoma/patologia , Glioblastoma/secundário , Carcinogênese/patologia , Mitose/fisiologia , Ensaios Clínicos como Assunto/normas , Ensaios Clínicos como Assunto , Tomografia/instrumentaçãoRESUMO
DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is a kinase with multiple implications for embryonic development, especially in the nervous system where it regulates the balance between proliferation and differentiation of neural progenitors. The DYRK1A gene is located in the Down syndrome critical region and may play a significant role in the developmental brain defects, early neurodegeneration, and cancer susceptibility of individuals with this syndrome. DYRK1A is also expressed in adults, where it might participate in the regulation of cell cycle, survival, and tumorigenesis, thus representing a potential therapeutic target for certain types of cancer. However, the final readout of DYRK1A overexpression or inhibition depends strongly on the cellular context, as it has both tumor suppressor and oncogenic activities. Here, we will discuss the functions and substrates of DYRK1A associated with the control of cell growth and tumorigenesis with a focus on the potential use of DYRK1A inhibitors in cancer therapy.