Targeting MET amplification in Gastro-oesophageal (GO) malignancies and overcoming MET inhibitor resistance: challenges and opportunities

References

• Weinstein IB, and Joe AK. Mechanisms of disease: oncogene addiction—a rationale for molecular targeting in cancer therapy. Nature Clin Pract Oncol. 2006;3:448–457. DOI:10.1038/ncponc0558.
   PubMedGoogle Scholar
• Arora A, Scholar EM, Davis IJ, et al. Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther. 2005;315:971–979.
   PubMed Web of Science ®Google Scholar
• Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202.
   PubMed Web of Science ®Google Scholar
• Network CGAR. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169.
   PubMed Web of Science ®Google Scholar
• Bang Y-J, Van Custem 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. Lancet. 2010;376:687–697.
   PubMed Web of Science ®Google Scholar
• Hecht JR, Bang YJ, Qin SK, 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;34
   Google Scholar
• Tabernero J, Hoff PM, Shen L, 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;19:1372–1384.
   PubMed Web of Science ®Google Scholar
• Thuss-Patience PC, Shah MA, Ohtsu A, 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;18:640–653.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Kawazoe A, Yanez PE, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: initial findings of the global phase 3 KEYNOTE-811 study. J Clin Oncol. 2021;39(15):suppl 4013. DOI:10.1200/JCO.2021.39.15_suppl.4013.
   PubMed Web of Science ®Google Scholar
• Nakajima M, Sawada H, Yamada Y, et al. The prognostic significance of amplification and overexpression of c‐met and c‐erb B‐2 in human gastric carcinomas. Cancer: Interdiscip Int J Am Cancer Soc. 1999;85:1894–1902.
   Google Scholar
• Birchmeier C, Gherardi E. Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol. 1998;8:404–410.
   PubMed Web of Science ®Google Scholar
• Gherardi E, Birchmeier W, and Birchmeier C, et al. Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 2012;12:89–103. DOI:10.1038/nrc3205.
   PubMed Web of Science ®Google Scholar
• Birchmeier C, Birchmeier W, Gherardi E, et al. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915–925.
   PubMed Web of Science ®Google Scholar
• Inokuchi M, Otsuki S, Fujimori Y, et al. Clinical significance of MET in gastric cancer. World J Gastrointest Oncol. 2015;7:317.
   PubMed Web of Science ®Google Scholar
• Schmidt L, Duh FM, Chen F, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 1997;16:68–73.
   PubMed Web of Science ®Google Scholar
• Davis IJ, McFadden AW, Zhang Y, et al. Identification of the receptor tyrosine kinase c-Met and its ligand, hepatocyte growth factor, as therapeutic targets in clear cell sarcoma. Cancer Res. 2010;70:639–645.
   PubMed Web of Science ®Google Scholar
• Mesteri I, Schoppmann SF, Preusser M, et al. Overexpression of CMET is associated with signal transducer and activator of transcription 3 activation and diminished prognosis in oesophageal adenocarcinoma but not in squamous cell carcinoma. Eur J Cancer. 2014;50:1354–1360.
   PubMed Web of Science ®Google Scholar
• Tuynman JB, Lagarde SM, ten Kate FJW, et al. Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma. Br J Cancer. 2008;98:1102–1108.
   PubMed Web of Science ®Google Scholar
• Xu Y-P, Lin G, Sun XJ, et al. C-Met as a molecular marker for esophageal squamous cell carcinoma and its association with clinical outcome. J Cancer. 2016;7:587.
   PubMed Web of Science ®Google Scholar
• Janjigian YY, Tang LH, and Coit DH, et al. MET expression and amplification in patients with localized gastric cancer. Cancer Epidemiol Prev Biomarkers. 2011;20:1021–1027. DOI:10.1158/1055-9965.EPI-10-1080.
   PubMed Web of Science ®Google Scholar
• Huang T-J, Wang J-Y. Lin, S.-R, et al. Overexpression of the c-met protooncogene in human gastric carcinoma-correlation to clinical features. Acta Oncol. 2001;40:638–643.
   PubMed Web of Science ®Google Scholar
• Nessling M, Solinas‐Toldo S, and Wilgenbus KK, et al. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN, MET, WNT2, and ERBB2. Genes Chromosomes Cancer. 1998;23:307–316.
   PubMed Web of Science ®Google Scholar
• Lennerz JK, Kwak EL, and Ackerman A, et al. MET Amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol. 2011;29:4803. DOI:10.1200/JCO.2011.35.4928.
   PubMed Web of Science ®Google Scholar
• Kawakami H, and Okamoto I. MET-targeted therapy for gastric cancer: the importance of a biomarker-based strategy. Gastric Cancer. 2016;19:687–695. DOI:10.1007/s10120-015-0585-x.
   PubMed Web of Science ®Google Scholar
• Liu YJ, Shen D, Yin X, et al. HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma. Br J Cancer. 2014;110:1169–1178.
   PubMed Web of Science ®Google Scholar
• Deng N, Goh LK, Das K, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–684.
   PubMed Web of Science ®Google Scholar
• Lee HE, Kim MA, Lee HS, et al. MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome. Br J Cancer. 2012;107:325–333.
   PubMed Web of Science ®Google Scholar
• Strong VE, Song KY, Park CH, et al. Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram. Ann Surg. 2010;251:640–646.
   PubMed Web of Science ®Google Scholar
• Steinberg ML, Hwang B-J, and Tang L, et al. E-cadherin gene alterations in gastric cancers in different ethnic populations. Ethn Dis. 2008;18:S2–S4.
   Google Scholar
• Krishnaswamy S, Kanteti R, Duke-Cohan JS, et al. Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res. 2009;15:5714–5723.
   PubMed Web of Science ®Google Scholar
• Chung HC, Bang YG, Fuchs CS, et al. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021;17:491–501.
   PubMed Web of Science ®Google Scholar
• Graziano F, Galluicio N, Lorenzini P, et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol. 2011;29:4789–4795.
   PubMed Web of Science ®Google Scholar
• Takahashi N, Furuta K, Taniguchi H, 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.
   PubMedGoogle Scholar
• Toiyama Y, Yasuda H, Saigusa S, et al. Co‐expression of hepatocyte growth factor and c‐Met predicts peritoneal dissemination established by autocrine hepatocyte growth factor/c‐Met signaling in gastric cancer. Int J Cancer. 2012;130:2912–2921.
   PubMed Web of Science ®Google Scholar
• Hao N-B, Tang B, Wang GZ, et al. Hepatocyte growth factor (HGF) upregulates heparanase expression via the PI3K/Akt/NF-κB signaling pathway for gastric cancer metastasis. Cancer Lett. 2015;361:57–66.
   PubMed Web of Science ®Google Scholar
• Lee J-H, Han SU, Cho H, et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene. 2000;19:4947–4953.
   PubMed Web of Science ®Google Scholar
• Chen JD, Kearns S, and Porter T, et al. MET mutation and familial gastric cancer. J MEd Gen. 2001;38.
   Google Scholar
• Smolen GA, Sordella R, and Muir B, et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proceedings of the National Academy of Sciences. 2006;103:2316–2321.
   Google Scholar
• Carneiro F, Sobrinho‐Simões M. The prognostic significance of amplification and overexpression of c‐met and c‐erb B‐2 in human gastric carcinomas. Cancer. 2000;88:238–239.
   PubMed Web of Science ®Google Scholar
• Fan G, Zhang S, and Gao Y, et al. HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer. Genes Dev. 2016;30:1542–1557.
   PubMed Web of Science ®Google Scholar
• Dulak AM, Gubish CT, Stabile LP, et al. HGF-independent potentiation of EGFR action by c-Met. Oncogene. 2011;30:3625–3635.
   PubMed Web of Science ®Google Scholar
• Goyal L, Muzumdar MD, Zhu AX. Targeting the HGF/c-MET pathway in hepatocellular carcinoma. Clin Cancer Res. 2013;19:2310–2318.
   PubMed Web of Science ®Google Scholar
• Corso S, Giordano S. Cell-autonomous and non–cell-autonomous mechanisms of HGF/MET–driven resistance to targeted therapies: from basic research to a clinical perspective. Cancer Discov. 2013;3:978–992.
   PubMed Web of Science ®Google Scholar
• Kawakami H, Okamoto I, Okamoto W, et al. Targeting MET amplification as a new oncogenic driver. Cancers (Basel). 2014;6:1540–1552.
   PubMed Web of Science ®Google Scholar
• Vanden Bempt I, Van Loo P, Drijkoningen M, et al. Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing. J Clin Oncol. 2008;26:4869–4874.
   PubMed Web of Science ®Google Scholar
• Kawakami H, Okamoto I, Arao T, et al. MET amplification as a potential therapeutic target in gastric cancer. Oncotarget. 2013;4(9). DOI:10.18632/oncotarget.718.
   PubMedGoogle Scholar
• Kaji M, Yonemura Y, and Harada S, et al. Participation of c-met in the progression of human gastric cancers: anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells. Cancer Gene Ther. 1996;3:393.
   PubMed Web of Science ®Google Scholar
• Yashiro M, Chung YS, Inoue T, et al. Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination. Int J Cancer. 1996;67:289–293.
   PubMed Web of Science ®Google Scholar
• Rong S, Segal S, and Anver M, et al. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proceedings of the National Academy of Sciences. 1994;91:4731–4735.
   Google Scholar
• Wu C-W, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–315.
   PubMed Web of Science ®Google Scholar
• Zou HY, Li Q, Lee JH, et al. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012;11:1036–1047.
   PubMed Web of Science ®Google Scholar
• Rege-Cambrin G, Scaravaglio P, Carozzi F, et al. Karyotypic analysis of gastric carcinoma cell lines carrying an amplified c-met oncogene. Cancer Genet Cytogenet. 1992;64:170–173.
   PubMed Web of Science ®Google Scholar
• Smith JJ, D’Angelica MI. Surgical management of hepatic metastases of colorectal cancer. Hematol Oncol Clin North Am. 2015;29:61–84.
   PubMed Web of Science ®Google Scholar
• Koon EC, Ma PC, Salgia R, et al. Effect of a c-Met-specific, ATP-competitive small-molecule inhibitor SU11274 on human ovarian carcinoma cell growth, motility, and invasion. Int J Gynecologic Cancer. 2008;18:976–984.
   PubMed Web of Science ®Google Scholar
• Buchanan SG, Hendle J, Lee PS, et al. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009;8:3181–3190.
   PubMed Web of Science ®Google Scholar
• Klotz M, Schmid E, Steiner-Hahn K, et al. Preclinical evaluation of biomarkers for response monitoring to the MET inhibitor BAY-853474. Biomarkers. 2012;17:325–335.
   PubMed Web of Science ®Google Scholar
• Hong S-W, Jung KH, Park BH, et al. KRC-408, a novel c-Met inhibitor, suppresses cell proliferation and angiogenesis of gastric cancer. Cancer Lett. 2013;332:74–82.
   PubMed Web of Science ®Google Scholar
• Hughes PE, Yang Y, and Rex K, et al. AMG 337, a novel, potent and selective MET kinase inhibitor, has robust growth inhibitory activity in MET-dependent cancer models. Cancer Res. 2014;74(19):728.
   Google Scholar
• Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007;6:3314–3322.
   PubMed Web of Science ®Google Scholar
• Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67:4408–4417.
   PubMed Web of Science ®Google Scholar
• Okamoto W, Okamoto I, Arao T, et al. Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012;11:1557–1564.
   PubMed Web of Science ®Google Scholar
• Yang Y, Wu N, Shen J, et al. MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer. Gastric Cancer. 2016;19:778–788.
   PubMed Web of Science ®Google Scholar
• Jardim DLF, de Melo Gagliato D, Falchook GS, et al. MET aberrations and c-MET inhibitors in patients with gastric and esophageal cancers in a phase I unit. Oncotarget. 2014;5:1837.
   PubMedGoogle Scholar
• Du J, Wu X, and Tong X, et al. Circulating tumor DNA profiling by next generation sequencing reveals heterogeneity of crizotinib resistance mechanisms in a gastric cancer patient with MET amplification. Oncotarget. 2017;8:26281.
   PubMedGoogle Scholar
• Kwak EL, Ahronian LG, Siravegna G, et al. Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET -Amplified esophagogastric cancer. Cancer Discov. 2015;5:1271–1281.
   PubMed Web of Science ®Google Scholar
• Catenacci DVT, Henderson L, Xiao SY, et al. Durable complete response of metastatic gastric cancer with anti-Met therapy followed by resistance at recurrence. Cancer Discov. 2011;1:573–579.
   PubMed Web of Science ®Google Scholar
• Moss RA, Bothos JG, and Patel PH, et al. Final results from the phase I study of MetMAb, a monovalent antagonist antibody to the receptor Met, dosed as single agent and in combination with bevacizumab in patients with advanced solid malignancies. Cancer Res. 2011;71(8):4717.
   Google Scholar
• Shah MA, Cho JY, Huat ITB, et al. Randomized phase II study of FOLFOX±MET inhibitor, onartuzumab (O), in advanced gastroesophageal adenocarcinoma (GEC). J Clin oncol. 2015;33(3):suppl 2. DOI:10.1200/jco.2015.33.3_suppl.2.
   Web of Science ®Google Scholar
• Cunningham D, Bang YJ, and Taberno J, et al. MetGastric: a randomized phase III study of onartuzumab (MetMAb) in combination with mFOLFOX6 in patients with metastatic HER2-negative and MET-positive adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol 2013 . 31(15):suppl
   Web of Science ®Google Scholar
• Shah MA, Bang YJ, and Lordick F, et al. METGastric: a phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET+) adenocarcinoma of the stomach or gastroesophageal junction (GEC). J Clin Oncol. 2015;33(15):suppl.
   Web of Science ®Google Scholar
• Catenacci DVT, Tebbutt NC, Davidenko I, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1467–1482.
   PubMed Web of Science ®Google Scholar
• Doi T, Kang YK, Muro K, et al. A phase 3, multicenter, randomized, double-blind, placebo-controlled study of rilotumumab in combination with cisplatin and capecitabine (CX) as first-line therapy for Asian patients (pts) with advanced MET-positive gastric or gastroesophageal junction. J Clin Oncol. 2015;33(3):226. supp TPS. DOI:10.1200/jco.2015.33.3_suppl.tps226.
   PubMed Web of Science ®Google Scholar
• Liu L, Zeng W, Wortinger MA, et al. LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth. Clin Cancer Res. 2014;20:6059–6070.
   PubMed Web of Science ®Google Scholar
• Casaletto JB, Geddie ML, and Abu-Yousif AO, et al. MM-131, a bispecific anti-Met/EpCAM mAb, inhibits HGF-dependent and HGF-independent Met signaling through concurrent binding to EpCAM. Proceedings of the National Academy of Sciences. 2019;116:7533–7542.
   Google Scholar
• Rosen LS, Goldman JW, Algazi AP, et al. A first-in-human phase I study of a bivalent MET antibody, emibetuzumab (LY2875358), as monotherapy and in combination with erlotinib in advanced cancer. Clin Cancer Res. 2017;23:1910–1919.
   PubMed Web of Science ®Google Scholar
• Yoh K, Kojima T, Kojima T, et al. A phase I dose-escalation study of LY2875358, a bivalent MET antibody, given as monotherapy or in combination with erlotinib or gefitinib in Japanese patients with advanced malignancies. Invest New Drugs. 2016;34:584–595.
   PubMed Web of Science ®Google Scholar
• Shah MA, Wainberg ZA, Catenacci DVT, et al. Phase II study evaluating 2 dosing schedules of oral foretinib (GSK1363089), cMET/VEGFR2 inhibitor, in patients with metastatic gastric cancer. PLoS One. 2013;8:e54014 .
   PubMed Web of Science ®Google Scholar
• Kang Y-K, Muro K, Ryu MH, et al. A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second-or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs. 2014;32:355–361.
   PubMed Web of Science ®Google Scholar
• Gavine PR, Ren Y, Han L, et al. Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models. Mol Oncol. 2015;9:323–333.
   PubMed Web of Science ®Google Scholar
• Lee J, Kim ST, Kim K, et al. Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY umbrella trial. Cancer Discov. 2019;9:1388–1405.
   PubMed Web of Science ®Google Scholar
• Hong DS, LoRusso P, Hamid O, et al. Phase I study of AMG 337, a highly selective small-molecule MET inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2019;25:2403–2413.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Karaszewska B, Kang YK, et al. A Multicenter Phase II Study of AMG 337 in patients with MET -Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other MET -Amplified solid tumors. Clin Cancer Res. 2019;25:2414–2423.
   PubMed Web of Science ®Google Scholar
• Zang ZJ, Ong CK, Cutcutache I, et al. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res. 2011;71:29–39.
   PubMed Web of Science ®Google Scholar
• Wolf J, Seto T, Han JY, et al. Capmatinib (INC280) in METΔex14 -mutated advanced non-small cell lung cancer (NSCLC): efficacy data from the phase II GEOMETRY mono-1 study. J Clin Oncol. 2019;37(15):suppl 9004. DOI:10.1200/JCO.2019.37.15_suppl.9004.
   Google Scholar
• Paik PK, Felip E, Veillon R, et al. Tepotinib in Non–Small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med. 2020;383:931–943.
   PubMed Web of Science ®Google Scholar
• Shitara K, Yamazaki K, Tsushima T, et al. Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors. Jpn J Clin Oncol. 2020;50:859–866.
   PubMed Web of Science ®Google Scholar
• Bang Y, Su WC, Schuler M, et al. Phase 1 study of capmatinib in MET‐positive solid tumor patients: dose escalation and expansion of selected cohorts. Cancer Sci. 2020;111:536–547.
   PubMed Web of Science ®Google Scholar
• Lee J, Ou S-HI, Lee JM, et al. Gastrointestinal malignancies harbor actionable MET exon 14 deletions. Oncotarget. 2015;6:28211.
   PubMed Web of Science ®Google Scholar
• Asaoka Y, Tada M, Ikenoue T, et al. Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion. Biochem Biophys Res Commun. 2010;394:1042–1046.
   PubMed Web of Science ®Google Scholar
• Cepero V, Sierra JR, Corso S, et al. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res. 2010;70:7580–7590.
   PubMed Web of Science ®Google Scholar
• Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–536.
   PubMed Web of Science ®Google Scholar
• Diaz LA Jr, Williams RT, Wu J, et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012;486:537–540.
   PubMed Web of Science ®Google Scholar
• Qi J, McTigue MA, Rogers A, et al. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors. Cancer Res. 2011;71:1081–1091.
   PubMed Web of Science ®Google Scholar
• Xu Y, Peng Z, Li Z, et al. Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma. BMC Cancer. 2015;15:1–7.
   PubMed Web of Science ®Google Scholar
• Nagatsuma AK, Aizawa M, Kuwata T, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. 2015;18:227–238.
   PubMed Web of Science ®Google Scholar
• Tsugawa K, Yonemura Y, Hirono Y, et al. Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers: correlation to clinical features. Oncology. 1998;55:475–481.
   PubMed Web of Science ®Google Scholar
• Petti C, Picco G, Martelli ML, et al. Truncated RAF kinases drive resistance to MET inhibition in MET-addicted cancer cells. Oncotarget. 2015;6:221.
   PubMedGoogle Scholar
• Ponzetto C, Giordano S, Peverali F, et al. C-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene. 1991;6:553–559.
   PubMed Web of Science ®Google Scholar
• Cui JJ. Targeting receptor tyrosine kinase MET in cancer: small molecule inhibitors and clinical progress. J Med Chem. 2014;57:4427–4453.
   PubMed Web of Science ®Google Scholar
• Heist RS, Sequist LV, Borger D, et al. Acquired resistance to crizotinib in NSCLC with MET exon 14 skipping. J Thorac Oncol. 2016;11:1242–1245.
   PubMed Web of Science ®Google Scholar
• Bahcall M, Sim T, Paweletz CP, et al. Acquired MET D1228V mutation and resistance to MET inhibition in lung Cancer. Cancer Discov. 2016;6:1334–1341.
   PubMed Web of Science ®Google Scholar
• Ou SHI, Young L, Schrock AB, et al. Emergence of preexisting MET Y1230C mutation as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping. J Thorac Oncol. 2017;12:137–140.
   PubMed Web of Science ®Google Scholar
• Cui JJ, Tran-Dubé M, Shen H, et al. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal–epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem. 2011;54:6342–6363.
   PubMed Web of Science ®Google Scholar
• Shen B, Wu F, Ye J, et al. Crizotinib-resistant MET mutations in gastric cancer patients are sensitive to type II tyrosine kinase inhibitors. Future Oncol. 2019;15:2585–2593.
   PubMed Web of Science ®Google Scholar
• Frigault MM, Markovets A, and Nuttall B, et al. Mechanisms of acquired resistance to Savolitinib, a selective MET inhibitor in MET-amplified gastric cancer. JCO Precis Oncol. 2020;4:222–232.
   Web of Science ®Google Scholar
• Hunter KW, Amin R, Deasy S, et al. Genetic insights into the morass of metastatic heterogeneity. Nat Rev Cancer. 2018;18:211.
   PubMed Web of Science ®Google Scholar
• Pectasides E, Stachler MD, Derks S, et al. Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma. Cancer Discov. 2018;8:37–48.
   PubMed Web of Science ®Google Scholar
• Kwak EL, LoRusso P, and Hamid O, et al. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. Journal of Clinical Oncology. 2015;33(3):suppl 1.
   PubMed Web of Science ®Google Scholar
• Bell LN, Ward JL, Degawa-Yamauchi M, et al. Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity. Am J Physiol Endocrinol Metab. 2006;291(4):E843–E848. DOI:10.1152/ajpendo.00174.2006.
   PubMed Web of Science ®Google Scholar
• Rahimi N, Saulnier R, Nakamura T, et al. Role of hepatocyte growth factor in breast cancer: a novel mitogenic factor secreted by adipocytes. DNA Cell Biol. 1994;13:1189–1197.
   PubMed Web of Science ®Google Scholar
• Eterno V, Zambelli A, Pavesi L, et al. Dipose-derived mesenchymal stem cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling. Oncotarget. 2014;5(3):613. DOI:10.18632/oncotarget.1359.
   PubMedGoogle Scholar
• Ahn SY, Kim J, Kim MA, et al. Increased HGF expression induces resistance to c-MET tyrosine kinase inhibitors in gastric cancer. Anticancer Res. 2017;37:1127–1138.
   PubMed Web of Science ®Google Scholar
• Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432:332–337.
   PubMed Web of Science ®Google Scholar
• Pennacchietti S, Michieli P, Galluzzo M, et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell. 2003;3(4):347–361. DOI:10.1016/S1535-6108(03)00085-0.
   PubMed Web of Science ®Google Scholar
• Zhang Y-W, Su Y, and Volpert OV, et al. Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc Natl Acad Sci. 2003;100:12718–12723.
   Google Scholar
• Parikh AR, Leshchiner I, Elagina L, et al. Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med. 2019;25(9):1415–1421. DOI:10.1038/s41591-019-0561-9.
   PubMed Web of Science ®Google Scholar
• Sung H, Ferlay J, and Siegel R, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–239.
   PubMed Web of Science ®Google Scholar
• Al-Batran SE, Homann N, and Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948–1957.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the ToGA trial: a phase III study of trastuzumab added to standard chemotherapy in first-line HER2-positive advanced gastric cancer. J Clin Oncol. 2009;27(18):LBA4509. DOI:10.1200/jco.2009.27.18_suppl.lba4509.
   Web of Science ®Google Scholar
• Srivastava AK, Navas T, Herrick WG, et al. Effective implementation of novel MET pharmacodynamic assays in translational studies. Ann Transl Med. 5(1)
   PubMed Web of Science ®Google Scholar
• Huang F, Ma Z, Pollan S, et al. Quantitative imaging for development of companion diagnostics to drugs targeting HGF/MET. J Pathol: Clin Res. 2016;2(4):210–222. DOI:10.1002/cjp2.49.
   PubMedGoogle Scholar
• Garber K. MET inhibitors start on road to recovery. Nat Rev Drug Discov. 2014;13:563.
   PubMed Web of Science ®Google Scholar
• Finisguerra V, Di Conza G, Di Matteo M, et al. MET is required for the recruitment of anti-tumoural neutrophils. Nature. 2015;522(7556):349–353. DOI:10.1038/nature14407.
   PubMed Web of Science ®Google Scholar
• Cui J, Xia T, Xie D, et al. HGF/Met and FOXM1 form a positive feedback loop and render pancreatic cancer cells resistance to Met inhibition and aggressive phenotypes. Oncogene. 2016;35(36):4708–4718. DOI:10.1038/onc.2016.14.
   PubMed Web of Science ®Google Scholar
• Mekki MS, Mougel A, Vinchent A, et al. Hypoxia leads to decreased autophosphorylation of the MET receptor but promotes its resistance to tyrosine kinase inhibitors. Oncotarget. 2018;9(43):27039. DOI:10.18632/oncotarget.25472.
   PubMedGoogle Scholar
• Li H, Li CW, Li X, et al. MET inhibitors promote liver tumor evasion of the immune response by stabilizing PDL1. Gastroenterology. 2019;156(6):1849–1861. DOI:10.1053/j.gastro.2019.01.252.
   PubMed Web of Science ®Google Scholar
• Glodde N, Bald T, van den Boorn-Konijnenberg D, et al. Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy. Immunity. 2017;47(4):789–802. DOI:10.1016/j.immuni.2017.09.012.
   PubMed Web of Science ®Google Scholar
• Qi C, Qin Y, Liu D, et al. 1372 O CLDN 18.2-targeted CAR-T cell therapy in patients with cancers of the digestive system. Ann Oncol. 2021;32:S1040.
   Google Scholar
• Tchou J, Zhao Y, Levine BL, et al. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast Cancerc-Met-CAR T cells for breast cancer. Cancer Immunol Res. 2017;5(12):1152–1161. DOI:10.1158/2326-6066.CIR-17-0189.
   PubMed Web of Science ®Google Scholar
• Thayaparan T, Petrovic RM, Achkova DY, et al. CAR T-cell immunotherapy of MET-expressing malignant mesothelioma. Oncoimmunology. 2017;6(12):e1363137. DOI:10.1080/2162402X.2017.1363137.
   PubMed Web of Science ®Google Scholar
• Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419–2430. DOI:10.1056/NEJMoa2004413.
   PubMed Web of Science ®Google Scholar
• Vijayaraghavan S, Lipfert L, Chevalier K, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet bispecific antibody, induces receptor downmodulation and antitumor activity by monocyte/macrophage trogocytosisamivantamab induces EGFR/cMet downmodulation by Trogocytosis. Mol Cancer Ther. 2020;19(10):2044–2056. DOI:10.1158/1535-7163.MCT-20-0071.
   PubMed Web of Science ®Google Scholar
• Park K, Haura EB, and Leighl NB, et al. Amivantamab in EGFR exon 20 insertion–mutated non–small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol. 2021;39(30):3391–3402.
   PubMed Web of Science ®Google Scholar
• Murciano-Goroff YR, Kannan S, Chang JC, et al. Switching inhibitor class overcomes crizotinib resistance in a MET fusion-positive NSCLC with a novel acquired MET G1090A mutation. Cancer Res. 2022;82(12_Supplement):5239. DOI:10.1158/1538-7445.AM2022-5239.
   Google Scholar