Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: new evidences and old challenges
Braz. J. Pharm. Sci. (Online)
; 53(2): e16076, 2017. graf
Artigo
em Inglês
| LILACS
| ID: biblio-951898
Biblioteca responsável:
BR40.1
Localização: BR40.1
ABSTRACT
ABSTRACT Human epidermal receptors (HER1/2/3/4) belong to the class of receptor-type tyrosine kinases. After binding a ligand, dimerization, it will ocurr activation of intracellular kinases after two-dimensional and cytoplasmic tail reciprocal transphosphorylation. This transphosphorylation recruits signaling pathways such as Ras/Raf/MEK/Erk1-2, PI3-K/AKT and JAK/STAT, which can affect the cell cycle, cytoskeleton reorganization, apoptosis, metastasis, differentiation, angiogenesis and transcription. HER deregulation is found in epithelial, mesenchymal and nervous neoplasms and is associated with poor prognosis and tumor severity. Since HER are promiscuous proteins when subjected to mutations, resultant modifications confer cellular metabolic superiority and activate complex, interconnected and overlapping networks of cytoplasmic signaling. Moreover, overexpression of HER1/2 is involved in tumor resistance to radiation and anti-hormone therapies. Indeed, HER2 expression is up to 100-fold higher in 25-30% of invasive breast cancers. These characteristics support the development of resistance to anti-HER1/2 chemotherapy such as monoclonal antibodies and tyrosine kinase inhibitors. Then, the challenges in research with HER-positive cancers include planning therapeutic strategies against known resistance mechanisms and identifying novel mechanisms as a way to overcome and control cell growth and malignant progression.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Proteínas Tirosina Quinases
/
Biologia Molecular
/
Neoplasias
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Braz. J. Pharm. Sci. (Online)
Assunto da revista:
Farmacologia
/
Teraputica
/
Toxicologia
Ano de publicação:
2017
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
Instituição/País de afiliação:
Federal University of Ceará/BR
/
Federal University of Piauí/BR