Arizona Cancer Center, 1515 N. Campbell Avenue, Room 1969G, P.O. Box 245024, Tucson, AZ 85724, USA.
J Oncol. 2009;2009:804108. doi: 10.1155/2009/804108. Epub 2009 Jul 14.
Cancers of the esophagus and stomach present a major health burden worldwide. In the past 30 years we have witnessed some interesting shifts in terms of epidemiology of esophago gastric cancers. Regardless of a world region, the majority of patients diagnosed with esophageal or gastric cancers die from progression or recurrence of their disease. While there are many active cytotoxic agents for esophageal and stomach cancers, their impact on the disease course has been modest at best. Median survival for patients with advanced gastroesophageal cancer is still less than a year. Therefore, novel strategies, based on our understanding of biology and genetics, are desperately needed. Epidermal growth factor receptor (EGFR) pathway has been implicated in pathophysiology of many epithelial malignancies, including esophageal and stomach cancers. EGFR inhibitors, small molecule tyrosine kinase inhibitors and monoclonal antibodies, have been explored in patients with esophageal and gastric cancers. It appears that tumors of the distal esophagus and gastroesophageal junction (GEJ) may be more sensitive to EGFR blockade than distal gastric adenocarcinomas. Investigations looking into potential molecular predictors of sensitivity to EGFR inhibitors for patients with esophageal and GEJ cancers are ongoing. While we are still searching for those predictors, it is clear that they will be different from ones identified in lung and colorectal cancers. Further development of EGFR inhibitors for esophageal and GEJ cancers should be driven by better understanding of EGFR pathway disregulation that drives cancer progression in a sensitive patient population.
食管和胃的癌症在全球范围内造成了重大的健康负担。在过去的 30 年里，我们见证了食管胃癌症的流行病学方面的一些有趣变化。无论在世界的哪个地区，大多数被诊断为食管或胃癌症的患者都死于疾病的进展或复发。尽管有许多针对食管和胃癌症的活性细胞毒素药物，但它们对疾病进程的影响充其量只是适度的。晚期胃食管癌症患者的中位生存期仍不足一年。因此，迫切需要基于我们对生物学和遗传学的理解的新策略。表皮生长因子受体 (EGFR) 途径已被牵涉到许多上皮恶性肿瘤的病理生理学中，包括食管和胃癌症。EGFR 抑制剂、小分子酪氨酸激酶抑制剂和单克隆抗体已在食管和胃癌症患者中进行了探索。似乎远端食管和胃食管交界处 (GEJ) 的肿瘤对 EGFR 阻断比远端胃腺癌更敏感。正在对潜在的 EGFR 抑制剂对食管和 GEJ 癌症患者的敏感性的分子预测因子进行调查。虽然我们仍在寻找这些预测因子，但很明显，它们将与在肺癌和结直肠癌中确定的预测因子不同。进一步开发针对食管和 GEJ 癌症的 EGFR 抑制剂，应该基于对驱动敏感患者群体中癌症进展的 EGFR 途径失调的更好理解。
