Chemotherapy resistance and oncogene expression in non-small cell lung cancer
Chemotherapy resistance and oncogene expression in non-small cell lung cancer
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DOI：
10.1016/j.jtcvs.2006.10.019
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发表时间：
2007-02-01
影响因子：
6
通讯作者：
Luketich, James D.
中科院分区：
文献类型：
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作者：
d'Amato, Thomas A.;Landreneau, Rodney J.;Luketich, James D.
目的：对于已经切除的非小细胞肺癌患者，建议在不了解肿瘤特定生物学特性的情况下进行经验性化疗，许多患者可能不会受益。体外化疗耐药与某些肿瘤的临床无反应性相关，在肺癌中，化疗耐药是普遍存在的。多药化疗耐药和化疗耐药与分子标志物的关联described.Methods：化疗耐药的双药卡铂和紫杉醇，顺铂和诺维布林，顺铂和多西他赛，顺铂和吉西他滨，分析了4571例非小细胞肺癌肿瘤的极端耐药试验。化疗耐药性定义如下：极端耐药性，比中位化疗耐药性高1 SD;中度耐药性，介于中位和极端耐药性之间;低耐药性，比中位低1 SD。化疗耐药与DNA倍体测定流式细胞术，标志物p53和上皮生长因子receptor.Results：极端或中间耐药的肿瘤中注意到在30%的卡铂-紫杉醇，在24%的顺铂-Navelbline，在42%的顺铂-吉西他滨，在27%的顺铂-多西他赛。对至少一种药物的极端或中度耐药发生在74%的卡铂-紫杉醇、68%的顺铂-诺维布林、88%的顺铂-吉西他滨和68%的顺铂-多西他赛中。异倍体肿瘤对依托泊苷（53% vs 36%，P = 0.0002）和拓扑替康（48% vs 36%，P = 0.0094）的中度和极端化疗耐药率较高，对吉西他滨的中度或极端化疗耐药率较低（88% vs 81%，P = 0.0345）。p53阳性肿瘤对足叶乙甙的耐药率较高（57% vs 44%，P = .0009）和阿霉素（73% vs. 58%，P = .0324），对顺铂的中度或极度耐药率较低（44% vs 54%，P = .0125），卡铂（47% vs 57%，P = .0129），紫杉醇（47% vs 57%，P = .0056）和吉西他滨（78% vs 87%，P = .0108）。较少的上皮生长因子受体阳性肿瘤对顺铂（13%对26%，P = 0.0074）和卡铂（13%对30%，P = 0.0008）极度耐药。结论：非小细胞肺癌肿瘤培养物中多药化疗耐药是常见的，分子标志物与体外化疗耐药之间存在相关性。通过将这种测试整合到临床试验中进行临床验证似乎是必要的。
Objectives: Empiric chemotherapy for patients with non-small cell lung cancer who have undergone resection is recommended without knowledge of the tumor's specific biologic characteristics, and many patients may not benefit. In vitro chemotherapy resistance is associated with clinical unresponsiveness in some tumors, and in lung cancer, chemotherapy resistance is prevalent. Multiple-agent chemotherapy resistance and association of chemotherapy resistance with molecular markers are described.Methods: Chemotherapy resistance to doublets-carboplatin and paclitaxel, cisplatin and navelbline, cisplatin and docetaxel, and cisplatin and gemcitabine-was analyzed in 4571 non-small cell lung cancer tumors with the extreme drug resistance assay. Chemotherapy resistance is defined as follows: extreme drug resistance, 1 SD above the median chemotherapy resistance; intermediate drug resistance, between the median and extreme drug resistances; and low drug resistance, 1 SD below the median. Chemotherapy resistance was compared with DNA ploidy measured by flow cytometry, and markers p53 and epithelial growth factor receptor were assayed by immunohistochemistry.Results: Tumors with extreme or intermediate drug resistance were noted in 30% to carboplatin-paclitaxel, in 24% to cisplatin-navelbline, in 42% to cisplatin-gemcitabine, and in 27% to cisplatin-docetaxel. Extreme or intermediate drug resistance to at least one drug occurred in 74% to carboplatin-paclitaxel, in 68% to cisplatin-navelbline, in 88% to cisplatin-gemcitabine, and in 68% to cisplatin-docetaxel. More intermediate plus extreme chemotherapy resistances occurred in aneuploid tumors to etoposide (53% vs 36%, P = .0002) and topotecan (48% vs 36%, P = .0094), with less intermediate or extreme chemotherapy resistance to gemcitabine (88% vs 81%, P = .0345). p53-Positive tumors had more intermediate or extreme resistance to etoposide (57% vs 44%, P = .0009) and doxorubicin (73% vs. 58%, P = .0324) and less intermediate or extreme resistance to cisplatin (44% vs 54%, P = .0125), to carboplatin (47% vs 57%, P = .0129), to taxol ( 47% vs 57%, P = .0056), and to gemcitabine (78% vs 87%, P = .0108). Fewer epithelial growth factor receptor-positive tumors were extremely drug resistant to cisplatin (13% vs 26%, P = .0074) and carboplatin (13% v. 30%, P = .0008).Conclusions: Multi-drug chemotherapy resistance in non-small cell lung cancer tumor cultures is common, and associations between molecular markers and in vitro chemotherapy resistance are noted. Clinical validation through integration of such testing into clinical trials seems warranted.