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PNAS:应用抗体-化疗联合疗法,提高肺癌病人生存率

来源:生物谷 2015-02-09 09:39

                                                          

2015年2月9日讯  /生物谷BIOON/  --近日,著名国际期刊PNAS发表了美国科学家的一项最新研究成果,他们发现应用抗体-化疗联合疗法能够提高非小细胞肺癌病人的生存率,这种效应可能依赖于治疗过程中肿瘤的血管功能,并且提出将PIGF作为检测药效的生物标记以及将VEGFR1作为抵抗治疗的生物标记。
 
目前,研究发现在标准化疗方案中添加anti-VEGF抗体能够提高生存率,已经是一种被人们所接受的治疗晚期非小细胞肺癌的治疗策略。但是anti-VEGF抗体疗法增加生存率的具体机制仍不清楚。在对晚期非小细胞肺癌病人进行单独贝伐单抗治疗和贝伐单抗-carboplatin-紫杉醇联合治疗后,研究人员进行了基于动态CT的血管参数分析和血浆细胞因子分析,试图发现响应这种治疗手段以及抵抗这种治疗方法的潜在生物标记。研究人员发现anti-VEGF治疗方法会导致血浆中PIGF持续增加,因此PIGF可能是一个潜在的药效标记。同时也发现在使用联合疗法之前,高水平的可溶性VEGFR1与病人较差的生存率呈现相关性,因此VEGFR1可作为药效抵抗的标记。这项研究表明基于贝伐单抗的治疗方法可能与病人生存率提高相关,同时在治疗之后,肿瘤脉管系统以及血液均得到改善。研究人员基于研究结果进行了假设,他们提出在进行贝伐单抗治疗后,血管通透性过度降低可能对NSCLC病人的联合治疗结果产生负面影响。根据这项假设,研究人员应进行贝伐单抗的进一步剂量滴定研究来检验这种剂量效应对肿瘤脉管系统和治疗效率的影响。
 
综上所述,该文章发现提高非小细胞肺癌病人生存率的抗体-化疗联合疗法可能依赖于治疗过程中肿瘤的血管功能发挥作用,同时这些相关性研究对于选择可能从联合疗法中获益的NSCLC病人进行针对性治疗具有重要意义。(生物谷Bioon.com)
 
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Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer
 
Rebecca S. Heista,1,2, Dan G. Dudab,1, Dushyant V. Sahanic,1, Marek Ancukiewiczb, Panos Fidiasd,Lecia V. Sequista, Jennifer S. Temela, Alice T. Shawa, Nathan A. Pennelle, Joel W. Nealf, Leena Gandhig,Thomas J. Lynchh, Jeffrey A. Engelmana, and Rakesh K. Jainb,2
 
Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non-small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment-while reducing blood flow, volume, and permeability in the overall population-may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy.
 
 
 
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