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Gastric Cancer
Erschienen in: Gastric Cancer 4/2021

19.03.2021 | Review Article

Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?

verfasst von: Giandomenico Roviello, Giuseppe Aprile, Alberto D’Angelo, Luigi Francesco Iannone, Franco Roviello, Karol Polom, Enrico Mini, Martina Catalano

Erschienen in: Gastric Cancer | Ausgabe 4/2021

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Abstract

Gastric cancer is one of the most common malignancy worldwide. In unresectable or metastatic disease, the prognosis is poor and in generally less than a year. HER2 expression remains an important biomarker to lead the addition of trastuzumab to first-line systemic chemotherapy in unresectable or metastatic gastroesophageal adenocarcinoma. To date, a major issue is represented by resistance to trastuzumab developed during treatment, considering the not improved outcomes in this molecular subtype of gastroesophageal adenocarcinoma to other HER2 target strategies. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance to HER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Furthermore, we describe the prognostic value of new non-invasive screening methods, under development novel agents (e.g., HER2 antibody-drug conjugates and bispecific antibodies) and strategies with antitumor activity in early studies.
Literatur
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-86.
2.
Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19(9):1523–9.PubMedCrossRef
3.
Rugge M, Fassan M, Graham DY. Epidemiology of gastric cancer. Gastric Cancer Princ Pract. 2015. p. 23–34.
4.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRef
5.
Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016;388(10060):2654–64.PubMedCrossRef
6.
Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006;24:2903–9.PubMedCrossRef
7.
8.
Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38-49.PubMedCrossRef
9.
Zaanan A, Bouché O, Benhaim L, Buecher B, Chapelle N, Dubreuil O, et al. Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO. Dig Liver Dis. 2018;50(8):768–79.PubMedCrossRef
10.
Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–9.PubMedCentralCrossRef
11.
Riese DJ, Stern DF. Specificity within the EGF family/ErbB receptor family signaling network. BioEssays. 1998;20(1):41–8.PubMedCrossRef
12.
Van Der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol. 1994;10:251–337.PubMedCrossRef
13.
Iqbal N, Iqbal N. Human epidermal growth factor receptor 2 (HER2) in cancers: overexpression and therapeutic implications. Mol Biol Int. 2014;2014:1–9.CrossRef
14.
Padhy LC, Shih C, Cowing D, Finkelstein R, Weinberg RA. Identification of a phosphoprotein specifically induced by the transforming DNA of rat neuroblastomas. Cell. 1982;28:865–71.PubMedCrossRef
15.
Schechter AL, Stern DF, Vaidyanathan L, Decker SJ, Drebin JA, Greene MI, et al. The neu oncogene: an erb-B-related gene encoding a 1,85,000-Mr tumour antigen. Nature. 1984;312:513–6.PubMedCrossRef
16.
Lee JW, Soung YH, Seo SH, Kim SY, Park CH, Wang YP, et al. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12:57–61.PubMedCrossRef
17.
Hollywood DP, Hurst HC. A novel transcription factor, OB2-1, is required for overexpression of the proto-oncogene c-erbB-2 in mammary tumour lines. EMBO J. 1993;12:2369–75.PubMedPubMedCentralCrossRef
18.
19.
Neve RM, Lane HA, Hynes NE. The role of overexpressed HER2 in transformation. Ann Oncol. 2001;12:S9–13.PubMedCrossRef
20.
Ménard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8.PubMedCrossRef
21.
Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469–87.PubMedPubMedCentralCrossRef
22.
Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7(7):505–16.PubMedCrossRef
23.
Nahta R, Yuan LXH, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res. 2005;65:11118–28.PubMedCrossRef
24.
Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005;353:1652–4.PubMedCrossRef
25.
26.
Rüschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.PubMedCrossRef
27.
Lee S, de Boer WB, Fermoyle S, Platten M, Kumarasinghe MP. Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections. Histopathology. 2011;59:832–40.PubMedCrossRef
28.
29.
Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer -a systematic analysis of data from the literature. J Cancer. 2012;3:137–44.PubMedPubMedCentralCrossRef
30.
Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM. c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol. 2000;18:2201–9.PubMedCrossRef
31.
Yonemura Y, Tanaka M, Sasaki T, Fushida S, Kimura H, Ohoyama S. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51:1034–8.PubMed
32.
Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.PubMedCrossRef
33.
Wolff AC, Hammond MEH, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J. Clin. Oncol. 2007; p. 118–45.
34.
Drebin JA, Stern DF, Link VC, Weinberg RA, Greene MI. Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene. Nature. 1984;312:545–8.PubMedCrossRef
35.
Brufsky A. Trastuzumab-based therapy for patients with HER2-positive breast cancer: from early scientific development to foundation of care. Am J Clin Oncol Cancer Clin Trials. 2010;33(2):186–95.
36.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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. Lancet. 2010;376:687–97.PubMedCrossRef
37.
Hofmann M, Stoss O, Shi D, Büttner R, Van De Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology. 2008;52:797–805.PubMedCrossRef
38.
Ryu MH, Yoo C, Kim JG, Ryoo BY, Park YS, Park SR, et al. Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. Eur J Cancer. 2015;51:482–8.PubMedCrossRef
39.
Rivera F, Romero C, Jimenez-Fonseca P, Izquierdo-Manuel M, Salud A, Martínez E, et al. Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial. Cancer Chemother Pharmacol. 2019;83:1175–81.PubMedPubMedCentralCrossRef
40.
Gong J, Liu T, Fan Q, Bai L, Bi F, Qin S, et al. Optimal regimen of trastuzumab in combination with oxaliplatin/capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial. BMC Cancer. 2016;16(1):68.PubMedPubMedCentralCrossRef
41.
Kurokawa Y, Sugimoto N, Miwa H, Tsuda M, Nishina S, Okuda H, et al. Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer. 2014;110:1163–8.PubMedPubMedCentralCrossRef
42.
Takahari D, Chin K, Ishizuka N, Takashima A, Minashi K, Kadowaki S, et al. Multicenter phase II study of trastuzumab with S-1 plus oxaliplatin for chemotherapy-naïve, HER2-positive advanced gastric cancer. Gastric Cancer. 2019;22:1238–46.PubMedCrossRef
43.
ter Veer E, Creemers A, de Waal L, van Oijen MGH, van Laarhoven HWM. Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in human epidermal growth factor receptor 2-positive advanced oesophagogastric cancer: A meta-analysis. Int J Cancer. 2018;143:438–48.PubMedCrossRef
44.
Chaganty BKR, Lu Y, Qiu S, Somanchi SS, Lee DA, Fan Z. Trastuzumab upregulates expression of HLA-ABC and T cell costimulatory molecules through engagement of natural killer cells and stimulation of IFNγ secretion. Oncoimmunology. 2016;5(4):e1100790.PubMedCrossRef
45.
Janjigian YY, Chou JF, Simmons M, Momtaz P, Sanchez-Vega F, Shcherba M, et al. First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma (mEGA). J Clin Oncol. 2019;37:62–62.CrossRef
46.
Chung HC, Bang Y-J, Fuchs CS, Qin S-K, Satoh T, Shitara K, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Futur Oncol. 2020;17(5):491–501.CrossRef
47.
Xia W, Gerard CM, Liu L, Baudson NM, Ory TL, Spector NL. Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene. 2005;24:6213–21.PubMedCrossRef
48.
Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC—a randomized phase III trial. J Clin Oncol. 2016;34:443–51.PubMedCrossRef
49.
Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, et al. Pertuzumab plus trastuzumab 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. Lancet Oncol. 2018;19:1372–84.PubMedCrossRef
50.
von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, et al. Adjuvant Pertuzumab and Trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377:122–31.CrossRef
51.
Baselga J, Cortés J, Kim S-B, Im S-A, Hegg R, Im Y-H, et al. Pertuzumab plus Trastuzumab plus Docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.PubMedCrossRef
52.
Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res. 2007;13:4909–19.PubMedCrossRef
53.
Satoh T, Doi T, Ohtsu A, Tsuji A, Omuro Y, Mukaiyama A, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTA—a randomized, phase III study. J Clin Oncol. 2014;32:2039–49.PubMedCrossRef
54.
Barok M, Tanner M, Köninki K, Isola J. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett. 2011;306:171–9.PubMedCrossRef
55.
Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18:640–53.PubMedCrossRef
56.
Von Minckwitz G, Du Bois A, Schmidt M, Maass N, Cufer T, De Jongh FE, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: A German Breast Group 26/Breast International Group 03–05 study. J Clin Oncol. 2009;27:1999–2006.CrossRef
57.
Palle J, Tougeron D, Pozet A, Soularue E, Artru P, Leroy F, et al. Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study. Oncotarget. 2017;8:101383–93.PubMedPubMedCentralCrossRef
58.
Narita Y, Kadowaki S, Masuishi T, Taniguchi H, Takahari D, Ura T, et al. Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer. Oncol Lett. 2017;14:2545–51.PubMedPubMedCentralCrossRef
59.
Li Q, Jiang H, Li H, Xu R, Shen L, Yu Y, et al. Efficacy of trastuzumab beyond progression in HER2 positive advanced gastric cancer: A multicenter prospective observational cohort study. Oncotarget. 2016;7:50656–65.PubMedPubMedCentralCrossRef
60.
Horita Y, Nishino M, Sugimoto S, Kida A, Mizukami A, Yano M, et al. Phase II clinical trial of second-line weekly paclitaxel plus trastuzumab for patients with HER2-positive metastatic gastric cancer. Anticancer Drugs. 2019;30:98–104.PubMedCrossRef
61.
Makiyama A, Sagara K, Kawada J, Kashiwada T, Hosokawa A, Horie Y, et al. A randomized phase II study of weekly paclitaxel ± trastuzumab in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer refractory to trastuzumab combined with fluoropyrimidine and platinum: WJOG7112G (T-ACT). J Clin Oncol. 2018;36:4011–4011.CrossRef
62.
Kijima T, Arigami T, Uenosono Y, Hiraki T, Yanagita S, Matsushita D, et al. Comparison of HER2 Status before and after Trastuzumab-based Chemotherapy in patients with advanced gastric cancer. Anticancer Res. 2020;40:75–80.PubMedCrossRef
63.
ZW25 Effective in HER2-positive cancers. Cancer Discov. 2019; p. 8.
64.
Meric-Bernstam F, Beeram M, Mayordomo JI, Hanna DL, Ajani JA, Blum Murphy MA, et al. Single agent activity of ZW25, a HER2-targeted bispecific antibody, in heavily pretreated HER2-expressing cancers. J Clin Oncol. 2018;36:2500–2500.CrossRef
65.
Stavenhagen JB, Gorlatov S, Tuaillon N, Rankin CT, Li H, Burke S, et al. Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcγ receptors. Cancer Res. 2007;67:8882–90.PubMedCrossRef
66.
Kim J, Fox C, Peng S, Pusung M, Pectasides E, Matthee E, et al. Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma. J Clin Invest. 2014;124:5145–58.PubMedPubMedCentralCrossRef
67.
Catenacci DVT, Kang YK, Park H, Uronis HE, Lee KW, Ng MCH, et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22–05): a single-arm, phase 1b–2 trial. Lancet Oncol. 2020;21:1066–76.PubMedCrossRef
68.
Catenacci DVT, Lim KH, Uronis HE, Kang Y-K, Ng MCH, Gold PJ, et al. Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC). J Clin Oncol. 2019;37:65–65.CrossRef
69.
70.
Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016;22:5097–108.PubMedCrossRef
71.
FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies. Case Med Res. 2019. http://​www.​fda.​gov.
72.
Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol Cancer Ther. 2018;17:1494–503.PubMedCrossRef
73.
Shi J, Li F, Yao X, Mou T, Xu Z, Han Z, et al. The HER4-YAP1 axis promotes trastuzumab resistance in HER2-positive gastric cancer by inducing epithelial and mesenchymal transition. Oncogene. 2018;37:3022–38.PubMedPubMedCentralCrossRef
74.
Shitara K, Iwata H, Takahashi S, Tamura K, Park H, Modi S, et al. Trastuzumab deruxtecan (DS-8201a)in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20:827–36.PubMedCrossRef
75.
Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol. 2017;18:1512–22.PubMedCrossRef
76.
Shitara K, Bang Y-J, Iwasa S, Sugimoto N, Ryu M-H, Sakai D, et al. Trastuzumab Deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382:2419–30.PubMedCrossRef
77.
Takegawa N, Tsurutani J, Kawakami H, Yonesaka K, Kato R, Haratani K, et al. [fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification. Int J Cancer. 2019;145:3414–24.PubMedCrossRef
78.
Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107:1039–46.PubMedPubMedCentralCrossRef
79.
Mitani S, Kawakami H. Emerging targeted therapies for HER2 positive gastric cancer that can overcome Trastuzumab resistance. Cancers (Basel). 2020;12(2):400.PubMedCentralCrossRef
80.
O’Donovan N, Byrne AT, O’Connor AE, McGee S, Gallagher WM, Crown J. Synergistic interaction between trastuzumab and EGFR/HER-2 tyrosine kinase inhibitors in HER-2 positive breast cancer cells. Invest New Drugs. 2011;29:752–9.PubMedCrossRef
81.
Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27:4702–11.PubMedPubMedCentralCrossRef
82.
Minkovsky N, Berezov A. BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr Opin Investig Drugs. 2008;9(12):1336–46.PubMed
83.
Sanchez-Vega F, Hechtman JF, Castel P, Ku GY, Tuvy Y, Won H, et al. Egfr and MET amplifications determine response to HER2 inhibition in ERBB2-amplified esophagogastric cancer. Cancer Discov. 2019;9–2:199–209.CrossRef
84.
Kim TY, Han HS, Lee KW, Zang DY, Rha SY, Park YI, et al. A phase I/II study of poziotinib combined with paclitaxel and trastuzumab in patients with HER2-positive advanced gastric cancer. Gastric Cancer. 2019;22:1206–14.PubMedCrossRef
85.
Oh DY, Lee KW, Cho JY, Kang WK, Im SA, Kim JW, et al. Phase II trial of dacomitinib in patients with HER2-positive gastric cancer. Gastric Cancer. 2016;19:1095–103.PubMedCrossRef
86.
Coutzac C, Pernot S, Chaput N, Zaanan A. Immunotherapy in advanced gastric cancer, is it the future? Crit Rev Oncol Hematol. 2019;133(25):25–32.PubMedCrossRef
87.
Satoh T, Kang YK, Chao Y, Ryu MH, Kato K, Cheol Chung H, et al. Exploratory subgroup analysis of patients with prior trastuzumab use in the ATTRACTION-2 trial: a randomized phase III clinical trial investigating the efficacy and safety of nivolumab in patients with advanced gastric/gastroesophageal junction cancer. Gastric Cancer. 2020;23:143–53.PubMedCrossRef
88.
Kelly RJ, Chung K, Gu Y, Steele KE, Rebelatto MC, Robbins PB, et al. Phase Ib/II study to evaluate the safety and antitumor activity of durvalumab (MEDI4736) and tremelimumab as monotherapy or in combination, in patients with recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. J Immunother Cancer. 2015;3:p157.PubMedCentralCrossRef
89.
Kelly RJ, Lee J, Bang Y-J, Almhanna K, Blum Murphy MA, Catenacci DVT, et al. Safety and efficacy of durvalumab in combination with tremelimumab, durvalumab monotherapy, and tremelimumab monotherapy in patients with advanced gastric cancer. J Clin Oncol. 2018;36:4031–4031.CrossRef
90.
Moehler M, Ryu MH, Dvorkin M, Lee KW, Coşkun H, Wong R, et al. Maintenance avelumab versus continuation of first-line chemotherapy in gastric cancer: JAVELIN Gastric 100 study design. Futur Oncol. 2019;15:567–77.CrossRef
91.
92.
Bang YJ, Yañez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, et al. Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: Primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018;29:2052–60.PubMedPubMedCentralCrossRef
93.
Fornaro L, Vivaldi C, Parnofiello A, Ugolini C, Aprile G, De Maglio G, et al. Validated clinico-pathologic nomogram in the prediction of HER2 status in gastro-oesophageal cancer. Br J Cancer. 2019;120:522–6.PubMedPubMedCentralCrossRef
94.
Lee HE, Park KU, Yoo SB, Nam SK, Park DJ, Kim HH, et al. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer. 2013;49:1448–57.PubMedCrossRef
95.
Palle J, Rochand A, Pernot S, Gallois C, Taïeb J, Zaanan A. Human Epidermal Growth Factor Receptor 2 (HER2) in advanced gastric cancer: current knowledge and future perspectives. Drugs. 2020;80(4):401–15.PubMedCrossRef
96.
Bozzetti C, Negri FV, Lagrasta CA, Crafa P, Bassano C, Tamagnini I, et al. Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer. 2011;104:1372–6.PubMedPubMedCentralCrossRef
97.
Park SR, Park YS, Ryu MH, Ryoo BY, Woo CG, Jung HY, et al. Extra-gain of HER2-positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: results of GASTric cancer HER2 reassessment study 1 (GASTHER1). Eur J Cancer. 2016;53:42–50.PubMedCrossRef
98.
Deguchi Y, Okabe H, Oshima N, Hisamori S, Minamiguchi S, Muto M, et al. PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma. Gastric Cancer. 2017;20:416–27.PubMedCrossRef
99.
Kim C, Lee CK, Chon HJ, Kim JH, Park HS, Heo SJ, et al. PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer. Oncotarget. 2017;8:113494–501.PubMedPubMedCentralCrossRef
100.
Huang LT, Ma JT, Zhang SL, Li XH, Sun L, Jing W, et al. Durable clinical response to Pyrotinib after resistance to prior anti-HER2 therapy for HER2-positive advanced gastric cancer: a case report. Front Oncol. 2019;9:1453.PubMedPubMedCentralCrossRef
101.
Minuti G, Cappuzzo F, Duchnowska R, Jassem J, Fabi A, Obrien T, et al. Increased MET and HGF gene copy numbers are associated with trastuzumab failure in HER2-positive metastatic breast cancer. Br J Cancer. 2012;107:793–9.PubMedPubMedCentralCrossRef
102.
Takahashi N, Furuta K, Taniguchi H, Sasaki Y, Shoji H, Honma Y, et al. Serum level of hepatocyte growth factor is a novel marker of predicting the outcome and resistance to the treatment with trastuzumab in HER2-positive patients with metastatic gastric cancer. Oncotarget. 2016;7:4925–38.PubMedCrossRef
103.
Kwak EL, Ahronian LG, Siravegna G, Mussolin B, Godfrey JT, Clark JW, et al. Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET-Amplified esophagogastric cancer. Cancer Discov. 2015;5:1271–81.PubMedPubMedCentralCrossRef
104.
105.
Pietrantonio F, Fuca G, Morano F, Gloghini A, Corso S, Aprile G, et al. Biomarkers of primary resistance to trastuzumab in HER2-positive metastatic gastric cancer patients: the AMNESIA case-control study. Clin Cancer Res. 2018;24:1082–9.PubMedCrossRef
106.
Zang ZJ, Ong CK, Cutcutache I, Yu W, Zhang SL, Huang D, et al. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res. 2011;71:29–39.PubMedCrossRef
107.
Ucar DA, Kurenova E, Garrett TJ, Cance WG, Nyberg C, Cox A, et al. Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth. Cell Cycle. 2012;11:3250–9.PubMedPubMedCentralCrossRef
108.
Arienti C, Zanoni M, Pignatta S, Del Rio A, Carloni S, Tebaldi M, et al. Preclinical evidence of multiple mechanisms underlying trastuzumab resistance in gastric cancer. Oncotarget. 2016;7:18424–39.PubMedPubMedCentralCrossRef
109.
Gambardella V, Gimeno-Valiente F, Tarazona N, Ciarpaglini CM, Roda D, Fleitas T, et al. Nrf2 through RPs6 activation is related to anti-HER2 drug resistance in HER2-amplified gastric cancer. Clin Cancer Res. 2019;25:1639–49.PubMedCrossRef
110.
Piro G, Carbone C, Cataldo I, Di Nicolantonio F, Giacopuzzi S, Aprile G, et al. An FGFR3 autocrine loop sustains acquired resistance to trastuzumab in gastric cancer patients. Clin Cancer Res. 2016;22:6164–75.PubMedCrossRef
111.
Pietrantonio F, Caporale M, Morano F, Scartozzi M, Gloghini A, De Vita F, et al. HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: implication for further clinical research. Int J Cancer. 2016;139:2859–64.PubMedCrossRef
112.
Mao L, Sun A-J, Wu J-Z, Tang J-H. Involvement of microRNAs in HER2 signaling and trastuzumab treatment. Tumor Biol. 2016;37(12):15437–46.CrossRef
113.
Sui M, Jiao A, Zhai H, Wang Y, Wang Y, Sun D, et al. Upregulation of miR-125b is associated with poor prognosis and trastuzumab resistance in HER2-positive gastric cancer. Exp Ther Med. 2017;14:657–63.PubMedPubMedCentralCrossRef
114.
Kim HP, Han SW, Song SH, Jeong EG, Lee MY, Hwang D, et al. Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired resistance to lapatinib in HER2-positive gastric cancer. Oncogene. 2014;33:3334–41.PubMedCrossRef
115.
Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, et al. Disrupting the interaction of BRD4 with Diacetylated twist suppresses Tumorigenesis in basal-like breast cancer. Cancer Cell. 2014;25:210–25.PubMedPubMedCentralCrossRef
116.
Arigami T, Uenosono Y, Hirata M, Yanagita S, Ishigami S, Natsugoe S. B7–H3 expression in gastric cancer: A novel molecular blood marker for detecting circulating tumor cells. Cancer Sci. 2011;102(5):1019–24.PubMedCrossRef
117.
Tsujiura M, Ichikawa D, Konishi H, Komatsu S, ShiozakiOtsuji AE. Liquid biopsy of gastric cancer patients: circulating tumor cells and cell-free nucleic acids. World J Gastroenterol. 2014;20(12):3265–86.PubMedPubMedCentralCrossRef
118.
Liu Y, Ling Y, Qi Q, Lan F, Zhu M, Zhang Y, et al. Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy. Mol Clin Oncol. 2017;6:235–42.PubMedPubMedCentralCrossRef
119.
Wang S, Zheng G, Cheng B, Chen F, Wang Z, Chen Y, et al. Circulating tumor cells (CTCs) detected by RT-PCR and its prognostic role in gastric cancer: a meta-analysis of published literature. PLoS One. 2014;9(6):e99259.PubMedPubMedCentralCrossRef
120.
Riquet M, Rivera C, Gibault L, Pricopi C, Mordant P, Badia A, et al. Extension lymphatique du cancer du poumon: une anatomie enchaînée dans des zones. Rev Pneumol Clin. 2014;70:16–25.PubMedCrossRef
121.
122.
Tseng JY, Yang CY, Liang SC, Liu RS, Jiang JK, Lin CH. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications. Cancers (Basel). 2014;6(4):2369–86.PubMedPubMedCentralCrossRef
123.
Nevisi F, Yaghmaie M, Pashaiefar H, Alimoghaddam K, Iravani M, Javadi G, et al. Correlation of HER2, MDM2, c-MYC, c-MET, and TP53 copy number alterations in circulating tumor cells with tissue in gastric cancer patients: a pilot study. Iran Biomed J. 2020;24:47–53.PubMedCrossRef
124.
Mishima Y, Matsusaka S, Chin K, Mikuniya M, Minowa S, Takayama T, et al. Detection of HER2 amplification in circulating tumor cells of HER2-negative gastric cancer patients. Target Oncol. 2017;12:341–51.PubMedCrossRef
125.
Akca H, Demiray A, Yaren A, Bir F, Koseler A, Iwakawa R, et al. Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer. Cancer Genet. 2013;206:73–80.PubMedCrossRef
126.
Neumann MHD, Bender S, Krahn T, Schlange T. ctDNA and CTCs in liquid biopsy-current status and where we need to progress. Comput Struct Biotechnol J. 2018;16:190–5.PubMedPubMedCentralCrossRef
127.
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24.PubMedPubMedCentralCrossRef
128.
Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479–91.PubMedCrossRef
129.
Sumbal S, Javed A, Afroze B, Zulfiqar HF, Javed F, Noreen S, et al. Circulating tumor DNA in blood: future genomic biomarkers for cancer detection. Exp Hematol. 2018;65:17–28.PubMedCrossRef
130.
Kinugasa H, Nouso K, Tanaka T, Miyahara K, Morimoto Y, Dohi C, et al. Droplet digital PCR measurement of HER2 in patients with gastric cancer. Br J Cancer. 2015;112:1652–5.PubMedPubMedCentralCrossRef
131.
Shoda K, Masuda K, Ichikawa D, Arita T, Miyakami Y, Watanabe M, et al. HER2 amplification detected in the circulating DNA of patients with gastric cancer: a retrospective pilot study. Gastric Cancer. 2015;18:698–710.PubMedCrossRef
132.
Maron SB, Chase LM, Lomnicki S, Kochanny S, Moore KL, Joshi SS, et al. Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma. Clin Cancer Res. 2019;25:7098–112.PubMedPubMedCentralCrossRef
133.
Wang H, Li B, Liu Z, Gong J, Shao L, Ren J, et al. HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer. Eur J Cancer. 2018;88:92–100.PubMedCrossRef
134.
Wang DS, Liu ZX, Lu YX, Bao H, Wu X, Zeng ZL, et al. Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer. Gut. 2019;68(7):1152–61.PubMedCrossRef
135.
Peng Z, Liu Y, Li Y, Zhang X, Zhou J, Lu M, et al. Serum HER2 extracellular domain as a potential alternative for tissue HER2 status in metastatic gastric cancer patients. Biomark Med. 2014;8:663–70.PubMedCrossRef
136.
Witzel I, Loibl S, Von Minckwitz G, Eidtmann H, Fehm T, Khandan F, et al. Predictive value of HER2 serum levels in patients treated with lapatinib or trastuzumab-a translational project in the neoadjuvant GeparQuinto trial. Br J Cancer. 2012;107:956–60.PubMedPubMedCentralCrossRef
137.
Lipton A, Leitzel K, Ali SM, Carney W, Platek G, Steplewski K, et al. Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. Cancer. 2011;117:5013–20.PubMedCrossRef
138.
O’Donoghue JA, Lewis JS, Pandit-Taskar N, Fleming SE, Schöder H, Larson SM, et al. Pharmacokinetics, biodistribution, and radiation dosimetry for 89 Zr-trastuzumab in patients with esophagogastric cancer. J Nucl Med. 2018;59:161–6.PubMedPubMedCentralCrossRef
139.
Bensch F, Brouwers AH, Lub-de Hooge MN, de Jong JR, van der Vegt B, Sleijfer S, et al. 89Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up. Eur J Nucl Med Mol Imaging. 2018;45:2300–6.PubMedPubMedCentralCrossRef
140.
Janjigian YY, Viola-Villegas N, Holland JP, Divilov V, Carlin SD, Gomes-DaGama EM, et al. Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and89Zr-trastuzumab PET. J Nucl Med. 2013;54:936–43.PubMedPubMedCentralCrossRef
141.
142.
Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell. 2018;172(373–386):e10.
143.
Nanki K, Toshimitsu K, Takano A, Fujii M, Shimokawa M, Ohta Y, et al. Divergent routes toward Wnt and R-spondin Niche independency during human gastric carcinogenesis. Cell. 2018;174(856–869):e17.
144.
Grün D, Van Oudenaarden A. Design and analysis of single-cell sequencing experiments. Cell. 2015;163(4):799–810.PubMedCrossRef
145.
Wang Q, Guldner IH, Golomb SM, Sun L, Harris JA, Lu X, et al. Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer. Nat Commun. 2019;10(1):3817.PubMedPubMedCentralCrossRef
146.
Shah MA, XuBangHoffLiuHerráez-Baranda RHYJPMTLA, et al. HELOISE: phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2–positive metastatic gastric or gast. J Clin Oncol. 2017;35(22):2558–67.PubMedCrossRef
Metadaten
Titel
Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?
verfasst von
Giandomenico Roviello
Giuseppe Aprile
Alberto D’Angelo
Luigi Francesco Iannone
Franco Roviello
Karol Polom
Enrico Mini
Martina Catalano
Publikationsdatum
19.03.2021
Verlag
Springer Singapore
Erschienen in
Gastric Cancer / Ausgabe 4/2021
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-021-01182-9

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