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转移性结直肠癌的精准医学:相关致癌途径与靶点——第1部分:靶向表皮生长因子受体和血管内皮生长因子的生物疗法

Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 1: Biologic Therapies Targeting the Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor.

作者信息

Weinberg Benjamin A, Hartley Marion L, Salem Mohamed E

出版信息

Oncology (Williston Park). 2017 Jul 15;31(7):539-48.

Abstract

The survival of patients with metastatic colorectal cancer has improved dramatically in recent years, with overall survival exceeding 3 years in large randomized clinical trials. There are now several treatment options for patients with metastatic colorectal cancer. In addition to chemotherapy backbones utilizing fluoropyrimidine, oxaliplatin, and irinotecan combinations, biologic agents that target specific oncogenic pathways have contributed to the improved survival observed in this patient population. This class of medications includes epidermal growth factor receptor (EGFR)-targeted drugs (cetuximab and panitumumab) and vascular endothelial growth factor (VEGF)-targeted therapies (bevacizumab, ramucirumab, ziv-aflibercept, and regorafenib). Bevacizumab remains the only VEGF-targeted agent approved by the US Food and Drug Administration in the first-line metastatic setting. EGFR-directed treatment should be restricted to patients with extended RAS and BRAF wild-type tumors. Tumor sidedness may be a more powerful prognostic and predictive biomarker than tumor mutational profile. Patients with left-sided primary tumors derive greater benefit from EGFR-targeted therapies whereas patients with right-sided primary tumors benefit more from bevacizumab. Herein we review drugs that target the EGFR and VEGF pathways, focusing on patient selection, drug toxicities, and how to choose agents for first-line therapy.

摘要

近年来,转移性结直肠癌患者的生存率有了显著提高,在大型随机临床试验中,总生存期超过了3年。目前,转移性结直肠癌患者有多种治疗选择。除了使用氟嘧啶、奥沙利铂和伊立替康联合的化疗方案外,针对特定致癌途径的生物制剂也有助于提高该患者群体的生存率。这类药物包括表皮生长因子受体(EGFR)靶向药物(西妥昔单抗和帕尼单抗)以及血管内皮生长因子(VEGF)靶向疗法(贝伐单抗、雷莫西尤单抗、阿柏西普和瑞戈非尼)。贝伐单抗仍然是美国食品药品监督管理局批准用于一线转移性治疗的唯一VEGF靶向药物。EGFR导向治疗应仅限于RAS和BRAF基因野生型肿瘤患者。肿瘤部位可能是比肿瘤突变谱更强有力的预后和预测生物标志物。左侧原发性肿瘤患者从EGFR靶向治疗中获益更大,而右侧原发性肿瘤患者从贝伐单抗中获益更多。在此,我们综述靶向EGFR和VEGF途径的药物,重点关注患者选择、药物毒性以及如何选择一线治疗药物。

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