课件：上海肿瘤医院王中华_晚期乳腺癌治疗2012.05.09讲.ppt

* Cartoon of Targets agents available ER / mTOR / VEGF / the HER family GF pathway is the topic of this talk They are linked * * * * As a dual-kinase inhibitor with specificity for both ErbB1 and ErbB2, lapatinib can block signaling through homodimers composed of either of these receptors.1,2 In theory, lapatinib may also be able to inhibit or decrease signaling through other heterodimer combinations, such as ErbB2/ErbB3. 1. Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 2001; 1:85-94. Xia W, Mullin RJ, Keith BR, et al. Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene 2002; 21:6255-63. * IDMC, Independent Data Monitoring Committee * * Overall survival data were immature at the time of presentation and median values were not reported. * * Overall survival data were immature at the time of presentation and median values were not reported. * * * * * * * Nonsteroidal inhibitors reversibly bind to the heme part of the aromatase enzyme complex. They bind noncovalently, and decrease estrogen production. Androgen molecules may displace inhibitors, thus restoring aromatase activity. Brueggemeier 1994/32/2/3, 34/1/1 The interaction between the enzyme and the inhibitor stabilizes aromatase and prevents its degradation. Blocking of proteolytic degradation causes an increase in the amount of aromatase present after administration of a nonsteroidal inhibitor. Harada et al 1999/216/2/3, 217/1/3 Steroidal inactivators mimic the natural substrate androstenedione. They bind covalently (irreversibly) to the aromatase substrate, causing inactivation of the enzyme, and are acted upon by the enzyme during the catalytic process. These agents cannot be replaced by androgen.Geisler 1998