乳腺癌分子靶向药物治疗进展资料.ppt

* * 可与 HER-2 受体胞外结构域 II 区结合，抑制二聚体的形成和受体介导的信号转导通路。 * Phase II trial presented at the American Society of Clinical Oncology (ASCO) 2008 meeting showed that half of the patients with advanced, HER2-positive metastatic breast cancer whose disease had progressed during a Herceptin-containing regimen benefited from a combination of Herceptin and pertuzumab. Reference Gelmon K et al. J Clin Oncol (Meeting Abstracts) 2008; 26: abs 1026. * 联合治疗的毒副反应如腹泻、恶心呕吐、黏膜炎、皮疹等发生率高于单一药物治疗，但仅腹泻为治疗相关的Ⅲ级以上毒副反应。Reference Gelmon K et al. J Clin Oncol (Meeting Abstracts) 2008; 26: abs 1026. * There are several strategies for inhibition of the erbB system currently in development. These include: Anti-ligand antibodies Monoclonal antibodies to erbB receptors that prevent ligand-binding, receptor  activation, and/or receptor internalization and degradation Bispecific antibodies that bind to receptors and immune cells, thus facilitating immunologic attack on cancer cells Ligand-toxin conjugates that bind specific receptors, introducing toxic compounds into cancer cells Antibody-toxin conjugates that bind to receptors Small molecule tyrosine kinase inhibitors that directly inhibit the receptor tyrosine kinase enzyme domain Anti-sense oligonucleotides that inhibit translation of ligand or receptor protein Monoclonal antibodies against erbB receptors and small molecule tyrosine kinase inhibitors are in the most advanced stages of clinical development. Importantly, those already approved for clinical use are agents that inhibit only a single receptor. (Balselga, 2002; Esteva, 2004; Holbro Hynes, 2004; Mendelsohn Baselga, 2003; Rowinsky, 2001; Zwick et al, 2001) * Lapatinib is a reversible small-molecule dual-kinase inhibitor targeting both ErbB1 and ErbB2 receptors. It works inside the cell by blocking the kinase activity of the receptor, and for this reason lapatinib can inhibit signaling through receptors that have lost or mutated their extracellular domains. I