Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas.

摘要: The activity and regulation of a number mitogenic signaling pathways is aberrant in astrocytomas, this thought to play crucial role the development these tumors. cascade events leading formation progression from low-grade high-grade astrocytomas well characterized. These include activating mutations, amplification, overexpression various growth factor receptors (e.g. epidermal receptor (EGFR), platelet derived (PDGFR), c-Met), intermediates Ras Protein kinase C (PKC)), cell cycle regulatory molecules mouse double minute-2 (Mdm2), cyclin-dependent kinase-4 (CDK4), CDK6), that positively regulate proliferation progression. Inactivating mutations deletions negatively p53, p16/INK4a, p14/ARF, p15/INK4b, retinoblastoma protein (Rb), Phosphatase tensin homologue deleted chromosome 10 (PTEN)) also participate actively transformed phenotype. Several are stimulated via an autocrine loop, with astrocytoma cells expressing both respective cognate ligand. Due multitude factors involved pathogenesis, attempts target single pathway have not given satisfactory results. simultaneous targeting several or intermediates, such as PKC, situated downstream many may show more efficacy therapy. We will give overview how combination aberrations drive into relentless constitute relevant therapeutic targets.