临床病理学限选课课件总结.pptVIP

做好靶向病理诊断提高临床肿瘤靶向治疗效率 目前上市的分子靶向药物仅对小部分人群有效，多数肿瘤患者未能获益。 同一种类型肿瘤中不是所有患者都存在药物作用的靶点，即使存在异常靶点，其异常情况也不完全相同。 如何通过预先的检查确定可能获益人群，有针对性的选择昂贵的分子靶向药物，是临床迫切需要解决的问题。 大部分肿瘤的分子学分型仍不健全或空白 分子靶向治疗超前于分子分型诊断 寻找药物疗效相关的分子靶点，明确分子靶点的变化对疗效的影响，进而指导个体化地分子靶向药物应用，将是临床研究的重点领域。对于这些靶点的检测就是临床病理医师的责任所在。 病理医师应与临床医师共享科技信息，在工作中密切配合，真正发挥好“病理为医之本”的作用。 随着对肿瘤细胞机制及信号传递途径的深入了解，结合病理分析，人们对肿瘤的治疗将会更具针对性 当前在肿瘤预防和诊疗方面已积累的丰富成果和资讯，将直接改变和影响肿瘤治疗效果。 病理医师在肿瘤诊断、治疗选择和预后判断的临床实践中起着不可替代的作用。 * * - The epidermal growth factor receptor (EGFR) is a transmembrane receptor with an intracellular tyrosine kinase domain, which is activated by growth factors. The main activating ligands are epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha).[1] - EGFR is a proto-oncogene and its activation plays a key role in the development of many cancers.[2] Activation occurs because of gene amplification, gene mutation and/or autocrine stimulation due to the overproduction of the EGFR ligands (e.g. EGF and TGF-alpha). Activation leads to the pairing of receptors with either another EGFR (homodimers) or another member of the EGFR family (heterodimers).[1] - Receptor dimerization initiates an intracellular signaling cascade, gene activation and the stimulation of cell cycle progression.[1] 1. Baselga J. Eur J Cancer 2001; 37 Suppl 4:S16–S22. 2. Yarden Y, Sliwkowski MX. Nat Rev Mol Cell Biol 2001; 2:127–137. * - Expression of EGFR has been observed in a variety of human tumors, both in vitro and in vivo.[1-15] The increased level of expression found in many tumor types and its consequences on tumor growth provide the rationale for targeting the EGFR in cancer therapy. - The level of EGFR expression varies widely with tumor type. In certain tumor types, EGFR expression is very common. - Variation in EGFR expression observed within studies of a given tumor type could be due in part to a lack of consistency in detection methods, inherent biological differences between tumors, and/or stage of disease. - High levels of EG