课件：抗血管生成药物在转移性结直肠癌中的应用.ppt

在结直肠癌中VEGF过度表达，研究显示，在腺瘤以及不同Dukes分期的腺癌中，VEGF-A及VEGFR-2的表达均持续高表达，贯穿整个肿瘤的发展过程。VEGF-A的表达更与肿瘤体积相关，肿瘤远处组织中VEGF-A的表达提高，可能促进之后的肿瘤扩散 研究显示，在结直肠癌中，VEGF的过度表达对患者的生存和预后产生负面影响 * 在结直肠癌中，血管生成与疾病进展，癌症复发转移和总生存下降相关 血管生成的重要性引发对抗增殖药物局限性的认识：抗增殖药物仅作用于肿瘤细胞，部分细胞可产生耐药，尽管抗细胞增殖药物可以杀死肿瘤细胞，但由于周围血管的支持，残存肿瘤细胞仍可获得血供而得以继续生长。同时，异常的肿瘤血管使药物向肿瘤组织内部递送减少，最终导致抗细胞增殖治疗的疗效受限。对肿瘤血管生成的重要性以及对抗增殖药物局限性的认识，使科学家们从肿瘤治疗的全局出发，建立了新的治疗策略。 肿瘤药物治疗的新策略是从全局出发，不仅针对肿瘤细胞，更要针对肿瘤血管生成，全方位地打击肿瘤，最大限度地控制和杀灭肿瘤。这种Anti-angiogenesis联合抗细胞增殖的策略（简称 A+策略）已在国际上成为肿瘤治疗的新核心策略 * 研究也证实了安维汀抑制VEGF的效应，在一项直肠癌患者的I期临床研究中，单剂安维汀注射后显示能显著降低微血管密度 研究也证实了安维汀抑制VEGF的效应，在一项直肠癌患者的I期临床研究中，单剂安维汀注射后显示能显著降低微血管密度，周细胞覆盖增加，组织间压下降(平均降低：从15.4 降至4.8mm Hg)，这提示安维汀能使肿瘤血管正常化。 While experimental support for the concept of normalisation continues to grow, it is not yet known exactly how anti-VEGF therapy helps improve the delivery of anticancer drugs. Nonetheless, such an improvement has been observed, and may provide a strong rationale for combining anti-VEGF therapy with other anticancer treatments to maximise overall effects of therapy.1,2 Some of the preclinical evidence suggesting that 安维汀 may improve delivery of chemotherapy includes a study reported by Wildiers et al.1 In this study, pretreatment with 安维汀 resulted in a 46% increase in intratumoural uptake of CPT-11 (irinotecan). Investigators concluded “anti-VEGF mAb definitely does not impair, and may even improve intratumoural uptake of CPT-11” in this murine tumour model. Investigators also found the improved uptake of CPT-11 remarkable in light of the fact that large vessel density (VD) was significantly decreased by anti-VEGF treatment in this study (P=0.09). They went on to postulate that “…although fewer vessels are present [after VEGF blockade], they are of better quality, likely allowing improved delivery of ‘bloodbourne agents’,” thereby adding more support behind the concept of anti-VEGF normalisation. Because of the small sample size in this study, it is not possible to draw definitive conclusions based on