Skip to main content

Advertisement

SpringerLink
Log in

Current and Future Biomarkers in Esophagogastric Adenocarcinoma

  • Review
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Biomarker-based therapies have shown improved patient outcomes across various cancer types. The purpose of this review to summarize our knowledge of current and future biomarkers in esophagogastric adenocarcinoma (EGA).

Methods

In this publication, we will review current standard biomarkers in patients with upper GI cancers. We will also discuss novel biomarkers that are under investigations and their associated therapies that are currently in clinical trials.

Results

EGAa are a group of heterogeneous diseases, both anatomically and molecularly. There are several established biomarkers (HER2, PD-L1, microsattelite instability or mismatch repair protein expression) that allow for individualized treatments for patients with these cancers. There are also several emerging biomarkers for EGA, some of which have clinically relevant associated therapies. Claudin 18.2 is the furthest along among these. Anti-claudin antibody, zolbetuximab, improved overall survival in biomarker select patients with advanced GEA in two phase 3 studies. Other novel biomarkers, such as FGFR2b and DKN01, are also in the process of validation, and treatments based on the presence of these biomarkers are currently in clinical studies.

Conclusion

Ongoing efforts to identify novel biomarkers in EGA have led to enhanced subclassification of upper GI cancers. These advances, coupled with the strategic application of targeted therapies and immunotherapy when appropriate, hold promise to further improve patients outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Daiko H, Kato K. Updates in the 8th edition of the TNM staging system for esophagus and esophagogastric junction cancer. Jpn J Clin Oncol 2020;50:847–851.

  3. Devaud N, Carroll P. Ongoing controversies in esophageal cancer II: gastrectomy versus esophagectomy for Siewert type II esophageal adenocarcinoma. Thorac Surg Clin. 2022;32:553–63.

    Article  PubMed  Google Scholar 

  4. Laurén P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. APMIS. 1965;64:31–49.

    Google Scholar 

  5. Nagtegaal ID, Odze RD, Klimstra D, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182–8.

    Article  PubMed  Google Scholar 

  6. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–75.

    Article  Google Scholar 

  7. Comprehensive molecular characterization of gastric adenocarcinoma. Cancer Genome Atlas Research N. Nature. 2014;513:202–9.

    Google Scholar 

  8. Bartley AN, Washington MK, Colasacco C, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35:446–64.

    Article  PubMed  CAS  Google Scholar 

  9. Dhakras P, Uboha N, Horner V, et al. Gastrointestinal cancers: current biomarkers in esophageal and gastric adenocarcinoma. Transl Gastroenterol Hepatol. 2020;5.

  10. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20:167–192.

  11. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    Article  PubMed  CAS  Google Scholar 

  12. 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;376:687–97.

    Article  PubMed  CAS  Google Scholar 

  13. Yang T, Xu R, You J, et al. Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer. BMC Cancer. 2022;22:1168.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ross DS, Zehir A, Cheng DT, et al. Next-generation assessment of human epidermal growth factor receptor 2 (ERBB2) amplification status: clinical validation in the context of a hybrid capture-based, comprehensive solid tumor genomic profiling assay. J Mol Diagn. 2017;19:244–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Janjigian YY, Kawazoe A, Yanez P, et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021;600:727–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. 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;19:1372–84.

    Article  PubMed  CAS  Google Scholar 

  17. 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;32:2039–49.

    Article  PubMed  CAS  Google Scholar 

  18. 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;18:640–53.

    Article  PubMed  CAS  Google Scholar 

  19. Makiyama A, Sukawa Y, Kashiwada T, et al. Randomized, phase II study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: WJOG7112G (T-ACT Study). J Clin Oncol. 2020;38:1919–27.

    Article  PubMed  CAS  Google Scholar 

  20. Seo S, Ryu MH, Park YS, et al. Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3). Gastric Cancer. 2019;22:527–35.

    Article  PubMed  CAS  Google Scholar 

  21. Pietrantonio F, Caporale M, Morano 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.

    Article  PubMed  CAS  Google Scholar 

  22. Kaito A, Kuwata T, Tokunaga M, et al. HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer. World J Clin Cases. 2019;7:1964–77.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Janjigian YY, Sanchez-Vega F, Jonsson P, et al. Genetic predictors of response to systemic therapy in esophagogastric cancer. Cancer Discov. 2018;8:49–58.

    Article  PubMed  CAS  Google Scholar 

  24. Haffner I, Schierle K, Raimundez E, et al. HER2 expression, test deviations, and their impact on survival in metastatic gastric cancer: results from the prospective multicenter VARIANZ study. J Clin Oncol. 2021;39:1468–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382:2419–30.

    Article  PubMed  CAS  Google Scholar 

  26. Van Cutsem E, di Bartolomeo M, Smyth E, et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol. 2023;24:744–56.

    Article  PubMed  Google Scholar 

  27. Yamaguchi K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: exploratory cohort results in a phase II trial. J Clin Oncol. 2023;41:816–25.

    Article  PubMed  CAS  Google Scholar 

  28. Thompson ED, Zahurak M, Murphy A, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017;66:794–801.

    Article  PubMed  CAS  Google Scholar 

  29. Wu C, Zhu Y, Jiang J, et al. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108:19–24.

    Article  PubMed  Google Scholar 

  30. Prince EA, Sanzari JK, Pandya D, et al. Analytical concordance of PD-L1 assays utilizing antibodies from FDA-approved diagnostics in advanced cancers: a systematic literature review. JCO Precis Oncol. 2021;5:953–73.

    Article  PubMed  Google Scholar 

  31. Ahn S, Kim KM. PD-L1 expression in gastric cancer: interchangeability of 22C3 and 28–8 pharmDx assays for responses to immunotherapy. Mod Pathol. 2021;34:1719–27.

    Article  PubMed  CAS  Google Scholar 

  32. Schoemig-Markiefka B, Eschbach J, Scheel AH, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer. 2021;24:1115–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Ye M, Huang D, Zhang Q, et al. Heterogeneous programmed death-ligand 1 expression in gastric cancer: comparison of tissue microarrays and whole sections. Cancer Cell Int. 2020;20:186.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Kalpakoff M, Hund S, Musser J, et al. Intrapatient tumor heterogeneity in IHC interpretation using PD-L1 IHC 22C3 pharmDx. Appl Immunohistochem Mol Morphol. 2021;29:667–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Zhou KI, Peterson B, Serritella A, et al. Spatial and temporal heterogeneity of PD-L1 expression and tumor mutational burden in gastroesophageal adenocarcinoma at baseline diagnosis and after chemotherapy. Clin Cancer Res. 2020;26:6453–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384:1191–203.

    Article  PubMed  CAS  Google Scholar 

  37. Janjigian YY, Shitara K, Moehler MH, et al. Nivolumab (NIVO) plus chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 3-year follow-up from CheckMate 649. J Clin Oncol. 2023;41:291–291.

    Article  Google Scholar 

  38.  Rha SY, Wyrwicz LS, Weber PEY, ... Bordia S, Bhagia P, Oh D-Y. Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer: phase III KEYNOTE-859 study. 2023.

  39. Patel MA, Kratz JD, Lubner SJ, et al. Esophagogastric cancers: integrating immunotherapy therapy into current practice. J Clin Oncol. 2022;40:2751–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Shitara K, Van Cutsem E, Bang YJ, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6:1571–80.

    Article  PubMed  Google Scholar 

  41. Shitara K, Ajani JA, Moehler M, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022;603:942–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Baudhuin LM, Burgart LJ, Leontovich O, et al. Use of microsatellite instability and immunohistochemistry testing for the identification of individuals at risk for Lynch syndrome. Fam Cancer. 2005;4:255–65.

    Article  PubMed  Google Scholar 

  43. Papke DJ Jr, Nowak JA, Yurgelun MB, et al. Validation of a targeted next-generation sequencing approach to detect mismatch repair deficiency in colorectal adenocarcinoma. Mod Pathol. 2018;31:1882–90.

    Article  PubMed  CAS  Google Scholar 

  44. Nowak JA, Yurgelun MB, Bruce JL, et al. Detection of mismatch repair deficiency and microsatellite instability in colorectal adenocarcinoma by targeted next-generation sequencing. J Mol Diagn. 2017;19:84–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Trabucco SE, Gowen K, Maund SL, et al. A novel next-generation sequencing approach to detecting microsatellite instability and pan-tumor characterization of 1000 microsatellite instability-high cases in 67,000 patient samples. J Mol Diagn. 2019;21:1053–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Amonkar M, Lorenzi M, Zhang J, et al. Structured literature review (SLR) and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) in gastric, colorectal, and esophageal cancers, American Society of Clinical Oncology. 2019.

  47. Zang YS, Dai C, Xu X, et al. Comprehensive analysis of potential immunotherapy genomic biomarkers in 1000 Chinese patients with cancer. Cancer medicine. 2019;8:4699–708.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Hause RJ, Pritchard CC, Shendure J, et al. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med. 2016;22:1342–50.

    Article  PubMed  CAS  Google Scholar 

  49. Fang W-L, Chen M-H, Huang K-H, et al. The clinicopathological features and genetic mutations in gastric cancer patients according to EMAST and MSI status. Cancers. 2020;12:551.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Chao J, Fuchs CS, Shitara K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol. 2021;7:895–902.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Janjigian YY, Shitara K, Moehler M, et al.  First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021.

  52. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38:1–10.

    Article  PubMed  CAS  Google Scholar 

  53. Andre T, Tougeron D, Piessen G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): the GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022;40:244–244.

    Article  Google Scholar 

  54. Pietrantonio F, Raimondi A, Lonardi S, et al. INFINITY: A multicentre, single-arm, multi-cohort, phase II trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). J Clin Oncol. 2023;41:358–358.

    Article  Google Scholar 

  55. Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14:7624–34.

    Article  PubMed  CAS  Google Scholar 

  56. Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2:285–93.

    Article  PubMed  CAS  Google Scholar 

  57. Tabariès S, Siegel PM. The role of claudins in cancer metastasis. Oncogene. 2017;36:1176–90.

    Article  PubMed  Google Scholar 

  58. Mitnacht-Kraus R, Kreuzberg M, Utsch M, et al. 378P-preclinical characterization of IMAB362 for the treatment of gastric carcinoma. Ann Oncol. 2017;28: v126.

    Article  Google Scholar 

  59. Pellino A, Brignola S, Riello E, et al.  Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas. J Pers Med. 2021;11.

  60. Shitara K, Lordick F, Bang YJ, et al: Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401:1655–1668.

  61. Klempner SJ, Lee KW, Shitara K, et al. ILUSTRO: phase II multicohort trial of zolbetuximab in patients with advanced or metastatic claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma. Clin Cancer Res. 2023;29:3882–3891.

  62. Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29:2133–2141.

  63. Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:1506–17.

    Article  PubMed  CAS  Google Scholar 

  64. Kubota Y, Kawazoe A, Mishima S, et al. Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer. ESMO Open. 2023;8:100762.

  65. Gao J, Wang Z, Jiang W, et al. CLDN18.2 and 4–1BB bispecific antibody givastomig exerts antitumor activity through CLDN18.2-expressing tumor-directed T-cell activation. J Immuno Cancer. 2023;11:e006704. 

  66. Overman MJ, Melhem R, Blum-Murphy MA, et al. A phase I, first-in-human, open-label, dose escalation and expansion study of PT886 in adult patients with advanced gastric, gastroesophageal junction, and pancreatic adenocarcinomas. J Clin Oncol. 2023;41:TPS765-TPS765.

  67. Wang Y, Gong J, Lin R, et al. First-in-human dose escalation and expansion study of SYSA1801, an antibody-drug conjugate targeting claudin 18.2 in patients with resistant/refractory solid tumors. J Clin Oncol. 2023;41:3016–3016.

  68. Qi C, Gong J, Li J, et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022;28:1189–1198.

  69. Katoh M, Katoh M. FGF signaling network in the gastrointestinal tract (review). Int J Oncol. 2006;29:163–8.

    PubMed  CAS  Google Scholar 

  70. Davies H, Hunter C, Smith R, et al. Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Res. 2005;65:7591–5.

    Article  PubMed  CAS  Google Scholar 

  71. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116–29.

    Article  PubMed  CAS  Google Scholar 

  72. Han N, Kim MA, Lee HS, et al. Evaluation of fibroblast growth factor receptor 2 expression, heterogeneity and clinical significance in gastric cancer. Pathobiology. 2015;82:269–79.

    Article  PubMed  CAS  Google Scholar 

  73. Ahn S, Lee J, Hong M, et al. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016;29:1095–103.

    Article  PubMed  CAS  Google Scholar 

  74. 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;18:227–38.

    Article  PubMed  CAS  Google Scholar 

  75. Klempner SJ, Madison R, Pujara V, et al. FGFR2-altered gastroesophageal adenocarcinomas are an uncommon clinicopathologic entity with a distinct genomic landscape. Oncologist. 2019;24:1462–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Su X, Zhan P, Gavine PR, et al. FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study. Br J Cancer. 2014;110:967–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Matsumoto K, Arao T, Hamaguchi T, et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer. 2012;106:727–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Gemo AT, Deshpande AM, Palencia S, et al. FPA144: a therapeutic antibody for treating patients with gastric cancers bearing FGFR2 gene amplification. Can Res. 2014;74:5446–5446.

    Article  Google Scholar 

  79. Catenacci DVT, Rasco D, Lee J, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol. 2020;38:2418–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Powers J, Palencia S, Foy S, et al. Abstract 1407: FPA144, a therapeutic monoclonal antibody targeting the FGFR2b receptor, promotes antibody dependent cell-mediated cytotoxicity and stimulates sensitivity to PD-1 in the 4T1 syngeneic tumor model. Can Res. 2016;76:1407–1407.

    Article  Google Scholar 

  81. Xiang H, Chan AG, Ahene A, et al. Preclinical characterization of bemarituzumab, an anti-FGFR2b antibody for the treatment of cancer. MAbs. 2021;13:1981202.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Wainberg ZA, Enzinger PC, Kang YK, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022;23:1430–40.

    Article  PubMed  CAS  Google Scholar 

  83. Shi T, Zhang Y, Wang Y, et al. DKK1 promotes tumor immune evasion and impedes anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer. Cancer Immunol Res. 2022;10:1506–24.

    Article  PubMed  CAS  Google Scholar 

  84. Klempner SJ, Sonbol BB, Wainberg ZA, et al. A phase 2 study (DisTinGuish) of DKN-01 in combination with tislelizumab + chemotherapy as first-line (1L) therapy in patients with advanced gastric or GEJ adenocarcinoma (GEA). J Clin Oncol. 2023;41:4027–4027.

    Article  Google Scholar 

  85. Kiyose S, Igarashi H, Nagura K, et al. Chromogenic in situ hybridization (CISH) to detect HER2 gene amplification in breast and gastric cancer: comparison with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Pathol Int. 2012;62:728–34.

    Article  PubMed  CAS  Google Scholar 

  86. Yan B, Yau EX, Choo SN, et al. Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples. J Clin Pathol. 2011;64:880–3.

    Article  PubMed  Google Scholar 

  87. Haas MS, Kagey MH, Heath H, et al. mDKN-01, a novel anti-DKK1 mAb, enhances innate immune responses in the tumor microenvironment. Mol Cancer Res. 2021;19:717–25.

    Article  PubMed  CAS  Google Scholar 

  88. Lee K-W, Moehler MH, Cunningham D, et al. Trial in progress: a phase 2, multicenter, open-label study of DKN-01 in combination with tislelizumab and chemotherapy as 1L therapy in patients with unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (G/GEJ; DisTinGuish). J Clin Oncol. 2023;41:TPS484-TPS484.

Download references

Funding

University of Wisconsin,Carbone Cancer Center,P30 CA014520,P30 CA014520

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, 53792, USA

    Ryan Sappenfield

  2. Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA

    Eric Mehlhaff, Devon Miller, Johnathan E. Ebben & Nataliya V. Uboha

  3. University of Wisconsin Carbone Cancer Center, 600 Highland Avenue, Madison, WI, 53792, USA

    Nataliya V. Uboha

Authors
  1. Ryan Sappenfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Mehlhaff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Devon Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johnathan E. Ebben
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nataliya V. Uboha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to writing and editting of the manuscript.

Corresponding author

Correspondence to Nataliya V. Uboha.

Ethics declarations

Competing Interests

Please review my updated COI on ASCO website. No COI for other authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sappenfield, R., Mehlhaff, E., Miller, D. et al. Current and Future Biomarkers in Esophagogastric Adenocarcinoma. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-023-01007-1

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12029-023-01007-1

Keywords

Search

Navigation