Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: new evidences and old challenges
AUTOR(ES)
Ferreira, Paulo Michel Pinheiro, Pessoa, Cláudia
FONTE
Braz. J. Pharm. Sci.
DATA DE PUBLICAÇÃO
20/07/2017
RESUMO
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.
Documentos Relacionados
- Gastrointestinal Cancers: Biology, Diagnosis, and Therapy
- Gastrointestinal Cancers: Biology, Diagnosis and Therapy
- Kinesin molecular motors: Transport pathways, receptors, and human disease
- Web-based access to mouse models of human cancers: the Mouse Tumor Biology (MTB) Database
- Human squamous cell lung cancers express increased epidermal growth factor receptors.