Publication Cover
Expert Review of Precision Medicine and Drug Development
Personalized medicine in drug development and clinical practice
Volume 2, 2017 - Issue 4
43
Views
0
CrossRef citations to date
0
Altmetric
Review

Precision medicine in gastric cancer: where are we now?

, &
Pages 193-204 | Received 01 Jun 2017, Accepted 17 Jul 2017, Published online: 27 Jul 2017

References

  • Cancer Research UK. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer [March] [2017]
  • Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11c–20.
  • Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209.
  • Ychou M, Boige V, Pignon JP, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–1721.
  • Stahl M, Walz MK, Stuschke M, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27:851–856.
  • Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–1820.
  • Cuschieri A, Fayers P, Fielding J, et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet. 1996;347:995–999.
  • Degiuli M, Sasako M, Ponti A, et al., Italian Gastric Cancer Study G. Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer. Br J Surg. 2014;101:23–31.
  • Songun I, Putter H, Kranenbarg EM, et al. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11:439–449.
  • Robertson CS, Chung SC, Woods SD, et al. A prospective randomized trial comparing R1 subtotal gastrectomy with R3 total gastrectomy for antral cancer. Ann Surg. 1994;220:176–182.
  • Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 2006;7:309–315.
  • Schuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28:5210–5218.
  • Yoshikawa T, Sasako M, Yamamoto S, et al. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009;96:1015–1022.
  • Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–3958.
  • Cunningham D, Starling N, Rao S, et al. Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.
  • Ter Veer E, Haj Mohammad N, Van Valkenhoef G, et al. The efficacy and safety of first-line chemotherapy in advanced esophagogastric cancer: a network meta-analysis. J Natl Cancer Inst. 2016 Aug 30;108(10).
  • Cunningham D, Stenning SP, Smyth EC, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017;18:357–370.
  • Okines AF, Langley RE, Thompson LC, et al. Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report. Ann Oncol. 2013;24:702–709.
  • Xiong BH, Cheng Y, Ma L, et al. An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer. Cancer Invest. 2014;32:272–284.
  • Janowitz T, Thuss-Patience P, Marshall A, et al. Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data. Br J Cancer. 2016;114:381–387.
  • 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. Lancet. 2010;376:687–697.
  • Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–1235.
  • Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–39.
  • Polkowski W, Van Sandick JW, Offerhaus GJ, et al. Prognostic value of Lauren classification and c-erbB-2 oncogene overexpression in adenocarcinoma of the esophagus and gastroesophageal junction. Ann Surg Oncol. 1999;6:290–297.
  • Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. Fourth ed. WHO Classification of Tumours, Volume 3. Lyon: International Agency for Research on Cancer. 2010.
  • Kakiuchi M, Nishizawa T, Ueda H, et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet. 2014;46:583–587.
  • Fareed KR, Ilyas M, Kaye PV, et al. Tumour regression grade (TRG) analyses in patients with resectable gastro-oesophageal adenocarcinomas treated with platinum-based neoadjuvant chemotherapy. Histopathology. 2009;55:399–406.
  • Fareed KR, Soomro IN, Hameed K, et al. Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy. World J Gastroenterol. 2012;18:1915–1920.
  • Lordick F, Ott K, Krause BJ, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8:797–805.
  • Ott K, Fink U, Becker K, et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol. 2003;21:4604–4610.
  • Ott K, Herrmann K, Schuster T, et al. Molecular imaging of proliferation and glucose utilization: utility for monitoring response and prognosis after neoadjuvant therapy in locally advanced gastric cancer. Ann Surg Oncol. 2011;18:3316–3323.
  • Herrmann K, Ott K, Buck AK, et al. Imaging gastric cancer with PET and the radiotracers 18F-FLT and 18F-FDG: a comparative analysis. J Nucl Med. 2007;48:1945–1950.
  • Fareed KR, Kaye P, Soomro IN, et al. Biomarkers of response to therapy in oesophago-gastric cancer. Gut. 2009;58:127–143.
  • Goekkurt E, Hoehn S, Wolschke C, et al. Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)–novel predictors for response and survival in gastric cancer patients. Br J Cancer. 2006;94:281–286.
  • Lu JW, Gao CM, Wu JZ, et al. Polymorphism in the 3ʹ-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy. J Hum Genet. 2006;51:155–160.
  • Liao Z, Liu H, Swisher SG, et al. Polymorphism at the 3ʹ-UTR of the thymidylate synthase gene: a potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys. 2006;64:700–708.
  • Ott K, Vogelsang H, Marton N, et al. The thymidylate synthase tandem repeat promoter polymorphism: a predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer. Int J Cancer. 2006;119:2885–2894.
  • Langer R, Specht K, Becker K, et al. Comparison of pretherapeutic and posttherapeutic expression levels of chemotherapy-associated genes in adenocarcinomas of the esophagus treated by 5-fluorouracil- and cisplatin-based neoadjuvant chemotherapy. Am J Clin Pathol. 2007;128:191–197.
  • Langer R, Specht K, Becker K, et al. Association of pretherapeutic expression of chemotherapy-related genes with response to neoadjuvant chemotherapy in Barrett carcinoma. Clin Cancer Res. 2005;11:7462–7469.
  • Wu X, Gu J, Wu TT, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 2006;24:3789–3798.
  • Zarate RN, Arias F, Bandres E, et al. Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy. World J Gastroenterol. 2006;12:6032–6036.
  • Ruzzo A, Graziano F, Kawakami K, et al. Pharmacogenetic profiling and clinical outcome of patients with advanced gastric cancer treated with palliative chemotherapy. J Clin Oncol. 2006;24:1883–1891.
  • Matsubara J, Nishina T, Yamada Y, et al. Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer. Br J Cancer. 2008;98:832–839.
  • Metzger R, Danenberg K, Leichman CG, et al. High basal level gene expression of thymidine phosphorylase (platelet-derived endothelial cell growth factor) in colorectal tumors is associated with nonresponse to 5-fluorouracil. Clin Cancer Res. 1998;4:2371–2376.
  • Kwon HC, Roh MS, Oh SY, et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007;18:504–509.
  • Letai AG. Diagnosing and exploiting cancer’s addiction to blocks in apoptosis. Nat Rev Cancer. 2008;8:121–132.
  • Igney FH, Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2:277–288.
  • Ludwig-Galezowska AH, Flanagan L, Rehm M. Apoptosis repressor with caspase recruitment domain, a multifunctional modulator of cell death. J Cell Mol Med. 2011;15:1044–1053.
  • Zhao L, Pan Y, Gang Y, et al. Identification of GAS1 as an epirubicin resistance-related gene in human gastric cancer cells with a partially randomized small interfering RNA library. J Biol Chem. 2009;284:26273–26285.
  • Miura JT, Johnston FM, Thomas J, et al. Molecular profiling in gastric cancer: examining potential targets for chemotherapy. J Surg Oncol. 2014;110:302–306.
  • Yoon HH, Bendell JC, Braiteh FS, et al. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial. Ann Oncol. 2016;27:2196–2203.
  • Tebbutt NC, Price TJ, Ferraro DA, et al. Panitumumab added to docetaxel, cisplatin and fluoropyrimidine in oesophagogastric cancer: ATTAX3 phase II trial. Br J Cancer. 2016;114:505–509.
  • Li J, Qin S, Xu J, et al. Double-blind, placebo-controlled phase iii trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016;34:1448–1454.
  • Bang YJ, Kang YK, Kang WK, et al. Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs. 2011;29:1449–1458.
  • Deng N, Goh LK, Wang H, 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.
  • Kim MA, Lee HS, Lee HE, et al. EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number. Histopathology. 2008;52:738–746.
  • 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. 2016;34:443–451.
  • Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al. Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients. J Clin Oncol. 2006;24:1612–1619.
  • Doi T, Muro K, Boku N, et al. Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol. 2010;28:1904–1910.
  • Yoon DH, Ryu MH, Park YS, et al. Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum. Br J Cancer. 2012;106:1039–1044.
  • Okines AF, Ashley SE, Cunningham D, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial. J Clin Oncol. 2010;28:3945–3950.
  • Lordick F, Kang YK, Chung HC, et al. Arbeitsgemeinschaft Internistische O and Investigators E. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–499.
  • Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial. Lancet Oncol. 2014;15:894–904.
  • Ou SH. Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): a better mousetrap? A review of the clinical evidence. Crit Rev Oncol Hematol. 2012;83:407–421.
  • Park YS, Hwang HS, Park HJ, et al. Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol. 2012;43:413–422.
  • Barros-Silva JD, Leitao D, Afonso L, et al. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 2009;100:487–493.
  • Satoh T, Xu RH, Chung HC, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: tyTAN–a randomized, phase III study. J Clin Oncol. 2014;32:2039–2049.
  • Isakoff SJ, Baselga J. Trastuzumab-DM1: building a chemotherapy-free road in the treatment of human epidermal growth factor receptor 2-positive breast cancer. Journal of Clinical Oncology. 2011;29:351–354.
  • Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. New England J Med. 2012;367:1783–1791.
  • 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 May;18(5):640-653.
  • Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–3976.
  • Van Cutsem E, De Haas S, Kang YK, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30:2119–2127.
  • Pavlakis N, Sjoquist KM, Martin AJ, et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): a multinational placebo-controlled phase II trial. J Clin Oncol. 2016;34:2728–2735.
  • Sun W, Powell M, O’Dwyer PJ, et al. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol. 2010;28:2947–2951.
  • Yi JH, Lee J, Lee J, et al. Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum. Br J Cancer. 2012;106:1469–1474.
  • Ohtsu A, Ajani JA, Bai YX, et al. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013;31:3935–3943.
  • Bang YJ, Im SA, Lee KW, et al. Randomized, double-blind phase II trial with prospective classification by ATM protein level to evaluate the efficacy and tolerability of olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer. J Clin Oncol. 2015;33:3858–3865.
  • Teng MW, Ngiow SF, Ribas A, et al. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–2145.
  • Romano E, Romero P. The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors. J Immunother Cancer. 2015;3:15.
  • Jin Z, Yoon HH. The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1. J Gastrointest Oncol. 2016;7:771–788.
  • Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
  • Derks S, Liao X, Chiaravalli AM, et al. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016;7:32925–32932.
  • Muro K, Chung HC, Shankaran V, et al. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016;17:717–726.
  • Janjigian YY, Bendell JC, Calvo EJWK, et al. CheckMate-032: phase I/II, open-label study of safety and activity of nivolumab (nivo) alone or with ipilimumab (ipi) in advanced and metastatic (A/M) gastric cancer (GC). 2016 ASCO annual meeting. 2016. J Clin Oncol. 2016;34(suppl):abstr 4010.
  • Kojima T, Hara H, Yamaguchi K . Phase II study of nivolumab (ONO-4538/BMS-936558) in patients with esophageal cancer: preliminary report of overall survival. 2016 Gastrointestinal Cancers Symposium. 2016.
  • Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;19(6):224ra24.
  • Thierry AR, Mouliere F, El Messaoudi S, et al. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med. 2014;20:430–435.
  • Heitzer E, Auer M, Ulz P, et al. Circulating tumor cells and DNA as liquid biopsies. Genome Med. 2013;5:73.
  • Wu CH, Lin SR, Yu FJ, et al. Development of a high-throughput membrane-array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers. Int J Cancer. 2006;119:373–379.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.