Lubner Sam J, Uboha Nataliya V, Deming Dustin A
Department of Medicine, Hematology-Oncology Section, University of Wisconsin Carbone Cancer Center, Madison, WI 53792, USA.
J Gastrointest Oncol. 2017 Jun;8(3):499-512. doi: 10.21037/jgo.2017.01.16.
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.
对癌症生物学认识的提高推动了胃肠道癌症治疗的进展。靶向血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）通路的药物引领了结肠癌治疗的发展。贝伐单抗、雷莫西尤单抗、西妥昔单抗和帕尼单抗等单克隆抗体（mAb）改善了结直肠癌的无进展生存期和总生存期（OS），并迅速得到应用。人表皮生长因子受体2（HER2）已证明对胃食管癌有显著益处，在HER2扩增的情况下，曲妥珠单抗联合化疗已成为标准治疗方案。然而，反应并不像曾经期望的那样持久和强烈。已经对这些生物化合物各自的耐药机制进行了假设，并且正在进一步阐明。本综述将探讨上述化合物的固有和获得性耐药机制。此外，我们将探索一些正在进行的临床试验，以利用耐药机制，希望能够实现靶向这些通路的前景。
