课件：胃癌靶向治疗.pptVIP

* * * * * Angiogenesis in tumor tissue is complex and includes molecular cross-talk between tumor cells, endothelial cells and, to a lesser extent, pericytes. Pathologic intracellular signaling in tumor cells is mediated by Growth factors and their receptors Activation of Ras Increased action of transcription factors Akt and Erk Activation of genes regulated by hypoxia-inducible factor-1 (HIF-1) Genes regulated by HIF-1 and overproduced by tumor cells include VEGF Cell survival factors IL-8 bFGF Ang-1 and Ang-2 These factors, particularly VEGF, bind to receptors on resident endothelial cells and induce cell migration, proliferation, permeability, and survival. * * * * 这是解离常数Kd和药时曲线下面积AUC的关系。Kd越小，表示亲和力越高，泰欣生为10-9级，西妥昔单抗为10-10级，泰欣生拥有相对中等的亲和力。 此图上的纵坐标表示AUC，纵坐标数值越大，表示在这个组织中的药物蓄积越厉害。 西妥昔单抗的皮肤肝脏和肿瘤的AUC值相差不大，表示其药物分子有很大一部分没有分布到肿瘤，被浪费掉了。 而泰欣生的肿瘤AUC很高，肝脏和皮肤的AUC相对较少，说明泰欣生药物分子绝大部分都分布到了肿瘤组织，而分布到皮肤和肝脏的很少，大部分药物被有效利用了。 因此，泰欣生拥有最合适的亲和力，对肿瘤的选择性高。 * * Eligibility criteria for the ToGA trial include: 18 years of age, HER2-positive histologically confirmed gastric cancer or gastro-oesophageal adenocarcinoma, with inoperable, locally advanced or recurrent and/or metastatic disease. The ToGA trial planned to recruit 584 patients. An additional 10 patients, who had already signed the informed consent form when the screening cut-off was reached, were allowed to enter the trial, resulting in a total of 594 patients recruited. The primary end point is overall survival in the two treatment arms. Secondary end points include progression-free survival, overall response rate, clinical benefit rate, duration of response and safety profile. * mTOR is a cytoplasmic serine/threonine kinase that functions as a central regulator of cellular metabolism, growth, proliferation, and angiogenesis1,2 mTOR is located at a control point between upstream signals and downstream effectors that promote protein synthesis3 and acts as a neoplastic switch that is turned on in pNET1,2 Insulin-like growth factor