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HER2 inhibition in gastro-oesophageal cancer:A review drawing on lessons learned from breast cancer

World Journal of Gastrointestinal Oncology 2018年第7期10卷 159-171页

作者： hazel lote Nicola Valeri Ian Chau Centre for Molecular Pathology Institute of Cancer Research Department of Medicine Royal Marsden Hospital

Human epidermal growth factor receptor 2(HER2)-inhibition is an important therapeutic strategy in HER2-amplified gastro-oesophageal cancer(GOC).A significant proportion of GOC patients display HER2 amplification,yet HER2 inhibition in these patients has not displayed the success seen in HER2 amplified breast *** of the current evidence surrounding HER2 has been obtained from studies in breast cancer,and we are only recently beginning to improve our understanding of HER2-amplified *** there are numerous licensed HER2 inhibitors in breast cancer,trastuzumab remains the only licensed HER2 inhibitor for HER2-amplified *** trials investigating lapatinib,trastuzumab emtansine,pertuzumab and MM-111 in GOC have demonstrated disappointing results and have not yet changed the treatment *** deruxtecan may hold promise and is currently being investigated in phase Ⅱ ***2 amplified GOC differs from breast cancer due to inherent differences in the HER2 amino-truncation and mutation rate,loss of HER2 expression,alterations in HER2 signalling pathways and differences in insulin-like growth factor-1 receptor and MET *** alterations involving different micro RNA profiles in GOC as compared to breast cancer and intrinsic differences in the immune environment are likely to play a *** key to effective treatment of HER2 amplified GOC lies in understanding these mechanisms and tailoring HER2 inhibition for GOC patients in order to improve clinical outcomes.

关键词： Human epidermal growth factor receptor 2 Gastro-oesophageal cancer Trastuzumab Resistance Biomarkers Breast cancer

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