西妥昔单抗
表皮生长因子受体
癌症研究
受体酪氨酸激酶
表皮生长因子受体抑制剂
酪氨酸激酶
单克隆抗体
MAPK/ERK通路
细胞周期蛋白依赖激酶8
生长因子受体
癌症
医学
生物
信号转导
抗体
内科学
受体
免疫学
细胞生物学
Notch信号通路
作者
Toni M. Brand,Mari Iida,Deric L. Wheeler
标识
DOI:10.4161/cbt.11.9.15050
摘要
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase belonging to the HER family of receptor tyrosine kinases. Receptor activation upon ligand binding leads to down stream activation of the PI3K/AKT, RAS/RAF/MEK/ERK and PLCγ/PKC pathways that influence cell proliferation, survival and the metastatic potential of tumor cells. Increased activation by gene amplification, protein overexpression or mutations of the EGFR has been identified as an etiological factor in a number of human epithelial cancers (e.g., NSCLC, CRC, glioblastoma and breast cancer). Therefore, targeting the EGFR has been intensely pursued as a cancer treatment strategy over the last two decades. To date, five EGFR inhibitors, including three small molecule tyrosine kinase inhibitors (TKIs) and two monoclonal antibodies have gained FDA approval for use in oncology. Both approaches to targeting the EGFR have shown clinical promise and the anti-EGFR antibody cetuximab is used to treat HNSCC and CRC. Despite clinical gains arising from use of cetuximab, both intrinsic resistance and the development of acquired resistance are now well recognized. In this review we focus on the biology of the EGFR, the role of EGFR in human cancer, the development of antibody-based anti-EGFR therapies and a summary of their clinical successes. Further, we provide an in depth discussion of described molecular mechanisms of resistance to cetuximab and potential strategies to circumvent this resistance.
科研通智能强力驱动
Strongly Powered by AbleSci AI