Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.
Phosphorylated AKT and MAPK expression in primary tumours and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.
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磷酸化的AKT和MAPK表达在原发性肿瘤以及接受伊立替康 - 盘妥昔单抗的结直肠癌患者中的相应转移和临床结果中。
DOI：
10.1186/1479-5876-10-71
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发表时间：
2012-04-10
影响因子：
7.4
通讯作者：
Cascinu S
中科院分区：
文献类型：
--
作者：
Scartozzi M;Giampieri R;Maccaroni E;Mandolesi A;Biagetti S;Alfonsi S;Giustini L;Loretelli C;Faloppi L;Bittoni A;Bianconi M;Del Prete M;Bearzi I;Cascinu S
临床观察表明，即使在不存在K-RAS基因突变的情况下，40%至70%的患者比例不可忽略，似乎也未从使用抗EGFR靶向抗体中获益。通过Ras-Raf-MAP-激酶和蛋白质-丝氨酸/苏氨酸激酶AKT的EGFR途径活化可确定对抗EGFR治疗的抗性。我们在接受伊立替康-西妥昔单抗治疗的K-RAS野生型患者中检测了结直肠肿瘤中磷酸化AKT和MAPK表达之间的相互作用以及相应的转移和总体结局。72例经组织学证实的转移性结直肠癌患者接受了基于伊立替康和西妥昔单抗的化疗，符合我们的分析条件。在转移灶中，pAKT与RR（9%对58%，p = 0.004）、PFS（2.3个月对9.2个月，p < 0.0001）和OS（6.1个月对26.7个月，p < 0.0001）相关，pMAPK与RR（10%对10%，p <0.001）相关，47%，p = 0.002）、PFS（2.3个月vs.8.6个月p < 0.0001）和OS（7.8个月vs.26个月p = 0.0004）。在多变量分析中，转移灶中的pAKT和pMAPK能够独立预测PFS。转移灶中的pAKT与RR独立相关，转移灶中的pAKT和pMAPK表达可调节EGFR靶向抗体的活性。我们可以推测，在pAKT和pMAPK转移的患者中，靶向这些因子的表达可能是至关重要的。
Clinical observations suggested that a non negligible proportion of patients, ranging from 40% to 70%, does not seem to benefit from the use of anti-EGFR targeted antibodies even in the absence of a mutation of the K- RAS gene. The EGFR pathway activation via the Ras-Raf-MAP-kinase and the protein-serine/threonine kinase AKT could determine resistance to anti-EGFR treatment. We tested the interaction between phosphorylated AKT and MAPK expression in colorectal tumours and corresponding metastases and global outcome in K-RAS wild type patients receiving irinotecan-cetuximab. Seventy-two patients with histologically proven metastatic colorectal cancer, treated with Irinotecan and Cetuximab based chemotherapy, were eligible for our analysis. In metastases pAKT correlated with RR (9% vs. 58%, p = 0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs., 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p = 0.0004). At multivariate analysis pAKT and pMAPK in metastases were able to independently predict PFS. pAKT in metastases independently correlated with RR as well pAKT and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAKT and pMAPK metastases expression targeting these factors may be crucial.
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影响因子：
8.8
作者：
Scartozzi, M.;Bearzi, I.;Mandolesi, A.;Giampieri, R.;Faloppi, L.;Galizia, E.;Loupakis, F.;Zaniboni, A.;Zorzi, F.;Biscotti, T.;Labianca, R.;Falcone, A.;Cascinu, S.
通讯作者：
Cascinu, S.
影响因子：
51.1
作者：
Moroni, M;Veronese, S;Bardelli, A
通讯作者：
Bardelli, A
影响因子：
6.4
作者：
Han, SW;Hwang, PG;Kim, NK
通讯作者：
Kim, NK
影响因子：
11.5
作者：
Lurje, Georg;Nagashima, Fumio;Lenz, Heinz-Josef
通讯作者：
Lenz, Heinz-Josef
影响因子：
45.3
作者：
Rothenberg, ML;LaFleur, B;Coffey, RJ
通讯作者：
Coffey, RJ