The genomics and therapeutics of HER2-positive gastric cancer-from trastuzumab and beyond Journal Article


Authors: Kelly, C. M.; Janjigian, Y. Y.
Article Title: The genomics and therapeutics of HER2-positive gastric cancer-from trastuzumab and beyond
Abstract: Gastric cancer is a biologically heterogeneous tumor. The identification of human epidermal growth factor receptor-2 (HER2) biomarker overexpression in gastric cancer represented a significant step towards unraveling the molecular complexity of this disease. Trastuzumab in combination with chemotherapy, in the first-line setting of patients with metastatic, HER2-positive gastric and gastroesophageal, represents the first targeted therapeutic to demonstrate improvement in response rate and survival in gastric cancer. However, not all patients with HER2-positive gastric cancer respond to trastuzumab and the majority of patients who do initially benefit from trastuzumab develop resistance to it. Advances in molecular oncology and cancer genomics have helped to classify gastric cancer into molecularly distinct subtypes. This information informs research efforts investigating the etiology of mechanisms of resistance to HER2-directed therapy and guides clinical investigation in methods to overcome this resistance. This article reviews anti-HER2-therapies that are currently used as standard of care in advanced, HER2-positive, breast cancer and are now under investigation as monotherapy and in combination with chemotherapy and/or a second HER2-directed agent in advanced HER2-positive gastric cancer. The future directions of clinical investigation in HER2-positive gastric cancer are also discussed including: novel HER2-directed therapies, the pharmacokinetics and pharmacodynamics of anti-HER2-therapies, the role of functional imaging, the potential of patient derived xenograft preclinical models and the importance of tumor genomic sequencing.
Keywords: inhibitor; genomics; trastuzumab; stomach neoplasms; phase-ii trial; kinase; epidermal-growth-factor; factor receptor; metastatic breast-cancer; prognostic-factor; patients pts; open-label; esophagogastric cancer; her2 status; esophagogastric junction neoplasms; oncogene protein; human epidermal growth factor receptor-2 (oncogene protein her2)
Journal Title: Journal of Gastrointestinal Oncology
Volume: 7
Issue: 5
ISSN: 2078-6891
Publisher: Pioneer Bioscience Publishing Company  
Date Published: 2016-10-01
Start Page: 750
End Page: 762
Language: English
ACCESSION: WOS:000392546900009
DOI: 10.21037/jgo.2016.06.10
PROVIDER: wos
PMCID: PMC5056254
PUBMED: 27747089
Notes: Review -- Source: Wos
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  1. Yelena Yuriy Janjigian
    395 Janjigian
  2. Ciara Marie Kelly
    90 Kelly