肝细胞癌分子靶向治疗研究进展演示文稿.pptVIP

Bisphosphonates Overview * Bisphosphonates Overview * * Bisphosphonates Overview * Role of angiogenesis in cancer development, growth and metastasis. A switch to an angiogenic phenotype is a prerequisite for the development from a premalignant stage to an invasive tumor. The neovascularization provides not only nutrients for tumor growth but also a large surface area of leaky vessels with incomplete basement membrane that facilitate intravasation of tumor cells. Tumor cells seeding in distant organs develop initially as avascular dormant micrometastases. Angiogenic switch leads to secondary angiogenesis and tumor growth, resulting in overt metastases (reprinted from Ref. [18] with permission of American Society of Clinical Oncology). Bisphosphonates Overview * HCC is characterized by a high propensity for vascular invasion, and the angiogenic activity of HCC correlates with the risk of vascular invasion[27].Angiogenesis inHCChasalsobeenfoundto correlate with metastasis [28]. The importance of angiogenesis in the progression of HCC implies the potential prognostic significance of assessment of angiogenesis in HCC. Studying the molecular mechanisms regulating angiogenesis in HCC provides insights intomolecular targets for antiangiogenic therapy inHCC. Bisphosphonates Overview * signaling pathways and potential drug targets to inhibit hepatocarcinogenesis. Activation of receptor tyrosine kinases by their ligands activates downstream signaling pathways with effects on angiogenesis, proliferation, migration and invasion, and apoptosis or survival of cells. Monoclonal antibodies inhibit ligand binding to the receptor and small?molecule tyrosine kinase inhibitors inhibit propagation of the downstream signal. * Multi-targeted agents represent a fertile area of research and development. * Bisphosphonates Overview * 多靶点、双通道激酶抑制剂，能够抑制RAF-1、B-RAF的丝氨酸/苏氨酸激酶活性，以及VGFR-2、VEGF-3、PDGF-β、KIT、FLT-3多种受体酪氨酸激酶的活性。 索拉非尼能够同时抗肿瘤血管生成及细胞增殖 1）阻断RAF/MEK/ERK介导的细胞信号传导通路，直接抑制肿瘤细胞的增殖； 2）作用于V