Unidad de Investigación, Hospital General Yagüe, Avenida del Cid 96, 09005, Burgos, Spain.
Mol Biol Rep. 2012 May;39(5):5387-91. doi: 10.1007/s11033-011-1337-6. Epub 2011 Dec 14.
Colorectal cancer is the third most prevalent cancer and a leading cause of cancer death. Metastatic colorectal cancer patients are treated with anti-EGFR monoclonal antibodies in combination with chemotherapy; however, the efficiency is only 10-20% of such patients. An increasing amount of data has demonstrated that response to anti-EGFR therapies is confined to patients with KRAS and BRAF wild type tumors but still some of these patients are non responders to this treatment. The presence of oncogenic deregulation of different members of EGFR downstream signaling or crosstalk molecules could predict the lack of response in these patients. In this study, 40 wild type KRAS and BRAF colorectal tumors were analyzed to elucidate whether PML-RARa bcr1 fusion gene may play a role in colorectal carcinogenesis. Specifically we want to determine if this fusion could be responsible for the inability to respond to anti-EGFR monoclonal antibodies. Here, for the first time it is reported, that PML-RARa bcr1 fusion is not responsible for colorectal tumor development and also, this translocation is not predicting the lack of efficacy of anti-EGFR therapies in wild type KRAS and BRAF colorectal cancer patients. These results also suggest that PML-RARa is unlikely to be a promising target for adjuvant therapy in colorectal cancer patients.
结直肠癌是第三大常见癌症，也是癌症死亡的主要原因。转移性结直肠癌患者接受抗 EGFR 单克隆抗体联合化疗治疗；然而，这种治疗方法的有效率只有 10-20%。越来越多的数据表明，抗 EGFR 治疗的反应仅限于 KRAS 和 BRAF 野生型肿瘤患者，但仍有一些患者对此治疗无反应。EGFR 下游信号转导或串扰分子的致癌失调的存在可以预测这些患者缺乏反应。在这项研究中，分析了 40 例 KRAS 和 BRAF 野生型结直肠肿瘤，以阐明 PML-RARa bcr1 融合基因是否可能在结直肠癌发生中起作用。具体来说，我们想确定这种融合是否会导致无法对抗 EGFR 单克隆抗体产生反应。在这里，首次报道 PML-RARa bcr1 融合与结直肠肿瘤的发展无关，并且这种易位也不能预测 KRAS 和 BRAF 野生型结直肠癌患者抗 EGFR 治疗的疗效缺失。这些结果还表明，PML-RARa 不太可能成为结直肠癌患者辅助治疗的有希望的靶点。
