内分泌治疗新思考.pptVIP

Thank you！ * * The classic mechanism of action of the ER is its nuclear function (also referred to as the genomic activity of the ER) consisting in the regulation of the expression of genes important for normal cell function but also tumor growth and survival. In addition to ER-mediated signaling, other growth factor-mediated signaling pathways also play a role in advanced breast cancer. There is crosstalk between the ER-mediated signaling pathway and other growth factor-mediated signaling pathways. The activation of the ER by growth factor-mediated signaling pathways is referred to as ligand-independent receptor activation. Enhanced growth factor-mediated signaling pathway activation can be related to abnormalities either at the transmembrane tyrosine kinase level or at the intracellular level (second messengers). An increasing number of targeted therapies blocking this pathway activation are already available or are still under development. * * * Growth-stimulating signals originating from within and outside the cell are integrated through mTOR into processes that maintain cell viability and stimulate cell growth, cell division, and angiogenesis. mTOR is a sensor that acts as a biochemical switch, ensuring that supplies of energy and nutrients in the cell are sufficient to support these processes1,2 In cancer cells, one or more of the proteins shown upstream of mTOR may be deregulated, and this loss of regulation contributes to, and in some cases drives, the malignancy. These include overproduction of hormones, cytokines, and growth factors and aberrant expression of growth factor receptors and signaling molecules, such as PI3-K, PTEN, Akt, and TSC1/2 (and LKB1, which is not shown). Aberrant signaling in parallel signaling pathways also affects signaling through mTOR because these pathways are connected to the mTOR pathway. These connections are referred to as “cross-talk” and involve the Ras/Raf/MAPK pathway and Abl signaling2-5 References Bjornsti and Houg