Integration of Epidermal Growth Factor Receptor Inhibitors with Preoperative Chemoradiation
Integration of Epidermal Growth Factor Receptor Inhibitors with Preoperative Chemoradiation
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DOI：
10.1158/1078-0432.ccr-09-1622
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发表时间：
2010-05-15
影响因子：
11.5
通讯作者：
Haustermans, Karin
中科院分区：
文献类型：
--
作者：
Debucquoy, Annelies;Machiels, Jean-Pascal;Haustermans, Karin
在许多不同类型的癌细胞中，表皮生长因子受体（EGFR）通路由于配体的过量产生、受体的过量产生或受体的组成性激活而变得过度激活。EGFR及其配体的过量产生与肺、结肠、卵巢等多种实体瘤的不良预后相关。这些观察结果导致了用于抗癌治疗的EGFR抑制剂的发展。在过去的几年中，EGFR抑制剂作为单一疗法或联合疗法在几种肿瘤类型中获得了令人鼓舞的结果。特别是，西妥昔单抗联合治疗头颈癌的治疗意图放疗比单独放疗增加中位生存期。同样，同样的方法可能对局部晚期直肠癌患者有益。不幸的是，首次将化疗与西妥昔单抗联合用于直肠癌的临床研究结果令人失望。转化研究表明，观察到的低反应率可能是由于西妥昔单抗的强抗增殖作用，可能损害了靶向增殖细胞的化疗药物的活性。这一结果表明，需要更多的转化研究来揭示如何操纵分子机制来优化联合治疗方案，并确定生物标志物，以选择那些将获得最大益处的患者。临床癌症研究；16 (10);2709 - 14所示。(c) 2010年aacr。
In many different cancer cell types, the epidermal growth factor receptor (EGFR) pathway becomes hyperactivated because of overproduction of the ligand, overproduction of the receptor, or constitutive activation of the receptor. The overproduction of EGFR and its ligands correlates with poor prognosis in several solid tumors such as lung, colon, and ovary. These observations led to the development of EGFR inhibitors for anticancer treatment. In the last few years, promising results have been obtained in several tumor types, with EGFR inhibitors given as monotherapy or in combined treatments. In particular, cetuximab in combination with curative-intent radiotherapy in head and neck cancer increases median survival over radiation alone. Similarly, the same approach might benefit patients with locally advanced rectal cancer. Unfortunately, the first clinical studies combining chemoradiation with cetuximab in rectal cancer gave disappointing results. Translational research suggested that the low response rate observed might have been due to the strong antiproliferative effect of cetuximab that may have compromised the activity of chemotherapeutics that target proliferating cells. This result indicates the need for more translational research to unravel how the molecular mechanisms might be manipulated to optimize the combined treatment regimen and to identify biomarkers that can select those patients who will derive most benefit. Clin Cancer Res; 16(10); 2709-14. (C) 2010 AACR.