Li Weiling, Zhang Xiaoling, Du Yunyi, Zhang Ying, Lu Jing, Hu Wenqing, Zhao Jun
Department of Oncology, Changzhi People's Hospital Affiliated to Changzhi Medical College, Changzhi, 046000, Shanxi, China.
Graduate School, Changzhi Medical College, Changzhi, 046000, Shanxi, China.
Biomark Res. 2022 Sep 30;10(1):71. doi: 10.1186/s40364-022-00416-x.
Recently, the global incidence of gastric/gastroesophageal junction (G/GEJ) cancer has remained high. China is also a large country with a high gastric cancer (GC) incidence rate, where the cases of GC account for 40% of all cases worldwide. More than 90% of GEJ cancers are the adenocarcinoma pathological type. Patients with early-stage G/GEJ adenocarcinoma may have a better prognosis after surgery. In contrast, patients with advanced metastatic G/GEJ adenocarcinoma usually choose comprehensive treatment based on systemic pharmacotherapy, but the subsequent long-term survival is not optimistic. The discovery of various biomarkers, especially microsatellite instability (MSI), programmed cell death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutational burden (TMB) and Epstein-Barr virus (EBV), has led to the identification of an increasing number of targeted populations and has greatly improved the clinical efficacy of treatments for G/GEJ adenocarcinoma. The ToGA trial added trastuzumab to standard chemotherapy, showed improved survival of patients with HER2-positive advanced G/GEJ adenocarcinoma and brought these patients into a new era of HER2-targeted therapy. Moreover, many HER2-targeted agents have been developed and studied in patients with advanced HER2-positive G/GEJ adenocarcinoma who have demonstrated excellent clinical outcomes. However, many patients experience disease progression with HER2-targeted therapy; hence, new anti-HER2 drugs keep being developed, significantly reducing HER2 resistance. This paper reviews HER2-targeted drugs for advanced metastatic G/GEJ adenocarcinoma, potential resistance mechanisms and future directions.
近年来，全球胃癌/胃食管交界（G/GEJ）癌发病率居高不下。中国也是胃癌（GC）高发大国，GC病例占全球所有病例的40%。超过90%的GEJ癌为腺癌病理类型。早期G/GEJ腺癌患者术后预后可能较好。相比之下，晚期转移性G/GEJ腺癌患者通常选择基于全身药物治疗的综合治疗，但随后的长期生存情况并不乐观。各种生物标志物的发现，尤其是微卫星不稳定性（MSI）、程序性细胞死亡配体1（PD-L1）、人表皮生长因子受体2（HER2）、肿瘤突变负荷（TMB）和爱泼斯坦-巴尔病毒（EBV），使得越来越多的靶向人群得以识别，并极大地提高了G/GEJ腺癌治疗的临床疗效。ToGA试验在标准化疗中加入曲妥珠单抗，显示HER2阳性晚期G/GEJ腺癌患者生存率提高，并使这些患者进入了HER2靶向治疗的新时代。此外，许多HER2靶向药物已被开发并在晚期HER2阳性G/GEJ腺癌患者中进行研究，均显示出优异的临床疗效。然而，许多患者在接受HER2靶向治疗后病情进展；因此，新的抗HER2药物不断被研发出来，显著降低了HER2耐药性。本文综述了晚期转移性G/GEJ腺癌的HER2靶向药物、潜在耐药机制及未来方向。
