Abstract:At present, gastric cancer is still the fifth largest malignant tumor in the world and the second largest cause of cancer-related death in the world. Previous studies have found that epidermal growth factor receptor 2 (HER2) positive gastric cancer is a special type of gastric cancer with worse prognosis. This kind of gastric cancer has a high expression of HER2 in the early stage of intraepithelial neoplasia, and the overexpression of HER2 increases significantly with the increase of the degree of dedifferentiation of precancerous lesions. With the emergence of targeted drugs such as Herceptin, the treatment of HER2 positive gastric cancer has taken a turn for the better. But Herceptin alone is not enough. The examination and treatment of HER2 positive gastric cancer are still in the primary level. In recent years, liquid biopsy techniques and a variety of therapeutic drugs are unveiling the mystery of HER2 positive gastric cancer step by step. Among them, the liquid biopsy technique is not only much more efficient than the traditional immunohistochemical technique, but also can monitor the curative effect of Trastuzumab dynamically in real time. This paper reviews the recent research progress of HER2 positive gastric cancer, including the treatment of HER2 positive gastric cancer, drug resistance and the relationship with immune status, so as to provide some reference for clinical practice.
[1] Kamangar F,Dores GM,Anderson WF. Patterns of cancer incidence,mortality,and prevalence across five continents:defining priorities to reduce cancer disparities in different geographic regions of the world [J]. J Clin Oncol,2006,24(14):2137-2150.
[2] Marrelli D,Polom K,Pascale V,et al. Strong prognostic value of microsatellite instability in intestinal type non-cardia gastric cancer [J]. Ann Surg Oncol,2016,23(3):943-950.
[3] Woll E,Eisterer W,Gerger A,et al. Treatment algorithm for patients with gastric adenocarcinoma:an austrian consensus on systemic therapy [J]. Anticancer Res,2019,39(9):4589-4596.
[4] Kaito A,Kuwata T,Tokunaga M,et al. HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer [J]. World J Clin Cases,2019,7(15):1964-1977.
[5] Oh DY,Bang YJ. HER2-targeted therapies—a role beyond breast cancer [J]. Nat Rev Clin Oncol,2020,17(1):33-48.
[6] 黄丹,李增山,樊祥山,等.中国人40842例胃腺癌HER2多中心检测结果分析[J].中华病理学杂志,2018,47(11):822-826.
[7] Albarello L,Pecciarini L,Doglioni C. HER2 testing in gastric cancer [J]. Adv Anat Pathol,2011,18(1):53-59.
[8] Bang YJ,Van Cutsem E,Feyereislova A,et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA):a phase 3,open-label,randomised controlled trial [J]. Lancet,2010,376(9742):687-697.
[9] Van Cutsem E,Bang YJ,Feng-Yi F,et al. HER2 screening data from ToGA:targeting HER2 in gastric and gastroesophageal junction cancer [J]. Gastric Cancer,2015,18(3):476-484.
[10] Wang H,Li B,Liu Z,et al. HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer [J]. Eur J Cancer,2018,88:92-100.
[11] Sun Y,Yu W,Guan W,et al. Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer [J]. Cancer Manag Res,2019,11:6397-6410.
[12] Wu X,Gu Z,Chen Y,et al. Application of PD-1 blockade in cancer immunotherapy [J]. Comput Struct Biotechnol J,2019,17:661-674.
[13] Fassan M,Brignola S,Pennelli G,et al. PD-L1 expression in gastroesophageal dysplastic lesions [J]. Virchows Arch,2020,477(1):151-156.
[14] Valentini AM,Di Pinto F,Coletta S,et al. Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however,not HER2 status [J]. Oncol Lett,2019,18(2):1775-1785.
[15] Bartley AN,Washington MK,Ismaila N,et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma:guideline summary from the College of American Pathologists,American Society for Clinical Pathology,and American Society of Clinical Oncology [J]. J Oncol Pract,2017,13(1):53-57.
[16] Qin S,Liu T,Li J. Reply to C. Kersten et al and D.A. Parikh et al [J]. J Clin Oncol,2019,37(18):1592-1593.
[17] Yuki S,Shinozaki K,Kashiwada T,et al. Multicenter phase Ⅱ study of SOX plus trastuzumab for patients with HER2(+) metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B [J]. Cancer Chemother Pharmacol,2020,85(1):217-223.
[18] Takahari D,Chin K,Ishizuka N,et al. Multicenter phase Ⅱ study of trastuzumab with S-1 plus oxaliplatin for chemotherapy-naive,HER2-positive advanced gastric cancer [J]. Gastric Cancer,2019,22(6):1238-1246.
[19] Tabernero J,Hoff PM,Shen L,et al. Pertuzumab plus tra-stuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB):final analysis of a double-blind,randomised,placebo-controlled phase 3 study [J]. Lancet Oncol,2018, 19(10):1372-1384.
[20] Shitara K,Hara H,Yoshikawa T,et al. Pertuzumab plus trastuzumab and chemotherapy for Japanese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subgroup analysis of the JACOB trial [J]. Int J Clin Oncol,2020,25(2):301-311.
[21] Kirschbrown WP,Wang B,Nijem I,et al. Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer [J]. Cancer Chemother Pharmacol,2019,84(3):539-550.
[22] Janjigian YY,Maron SB,Chatila WK,et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal,gastric,or gastro-oesophageal junction cancer:an open-label,single-arm,phase 2 trial [J]. Lancet Oncol,2020,21(6):821-831.
[23] Sampera A,Sanchez-Martin FJ,Arpi O,et al. HER-family ligands promote acquired resistance to trastuzumab in gastric cancer [J]. Mol Cancer Ther,2019,18(11):2135-2145.
[24] Canonici A,Ivers L,Conlon NT,et al. HER-targeted tyrosine kinase inhibitors enhance response to trastuzumab and pertuzumab in HER2-positive breast cancer [J]. Invest New Drugs,2019,37(3):441-451.
[25] Rugo HS,Di Palma JA,Tripathy D,et al. The characterization,management,and future considerations for ErbB-family TKI-associated diarrhea [J]. Breast Cancer Res Treat,2019,175(1):5-15.
[26] Nakata S,Fujita M,Nakanishi H. Efficacy of Afatinib and Lapatinib against HER2 gene-amplified Trastuzumab-sensitive and -resistant human gastric cancer cells [J]. Anticancer Res,2019,39(11):5927-5932.
[27] Li X,Yang C,Wan H,et al. Discovery and development of pyrotinib:a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer [J]. Eur J Pharm Sci,2017, 110:51-61.
[28] Blair HA. Pyrotinib:first global approval [J]. Drugs,2018, 78(16):1751-1755.
[29] Gao Z,Song C,Li G,et al. Pyrotinib treatment on HER2-positive gastric cancer cells promotes the released exosomes to enhance endothelial cell progression,which can be counteracted by apatinib [J]. Onco Targets Ther,2019, 12:2777-2787.
[30] Shitara K,Iwata H,Takahashi S,et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer:a dose-expansion,phase 1 study [J]. Lancet Oncol,2019,20(6):827-836.
[31] Bang YJ,Giaccone G,Im SA,et al. First-in-human phase 1 study of margetuximab (MGAH22),an Fc-modified chimeric monoclonal antibody,in patients with HER2-positive advanced solid tumors [J]. Ann Oncol,2017,28(4):855-861.
[32] Meric-Bernstam F,Zheng X,Shariati M,et al. Survival outcomes by TP53 mutation status in metastatic breast cancer [J]. JCO Precis Oncol,2018,2018:PO.17.00245.