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Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer 被引量:3

Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer
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摘要 Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade. Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.
出处 《World Journal of Clinical Oncology》 CAS 2016年第5期340-351,共12页 世界临床肿瘤学杂志(英文版)
关键词 EPIDERMAL GROWTH FACTOR RECEPTOR Oncogenic signature Kirsten RAS BRAF Cetuximab Panitumumab EPIDERMAL GROWTH FACTOR RECEPTOR BLOCKADE RESISTANCE Epidermal growth factor receptor Oncogenic signature Kirsten RAS BRAF Cetuximab Panitumumab Epidermal growth factor receptor blockade resistance
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  • 1Fang-Hua Li,Zhuang-Hua Li,Hui-Yan Luo,Miao-Zhen Qiu,Yu-Hong Li,Rui-Hua Xu,State Key Laboratory of Oncology in Southern China,Department of Medical Oncology,Sun YatSen University Cancer Center,Guangzhou 510060,Guangdong Province,China Fang-Hua Li,Department of Medical Oncology,Shengli Oil Field Central Hospital,Dongying 257034,Shandong Province,China Lin Shen,Department of GI Oncology,Peking University School of Oncology,Beijing Cancer Hospital and Institute,Beijing 100142,China Hui-Zhong Zhang,State Key Laboratory of Oncology in Southern China,Department of Pathology,Sun Yat-Sen University Cancer Center,Guangzhou 510060,Guangdong Province,China.Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer[J].World Journal of Gastroenterology,2010,16(46):5881-5888. 被引量:9

二级参考文献24

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