Targeting the fibroblast growth factor receptor 2 in gastric cancer: Promise or pitfall?

C. Hierro, M. Alsina, M. Sánchez, V. Serra, J. Rodon, J. Tabernero

Research output: Contribution to journalReview articleResearchpeer-review

13 Citations (Scopus)

Abstract

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Gastric cancer is the third leading cause of death from cancer worldwide. Systemic chemotherapy remains the mainstay therapeutic option for this poor prognosis cancer. Trastuzumab, the epidermal growth factor receptor 2 (ERBB2 or HER2)- antibody, is the only biological agent approved for the molecularly selected population of HER2-positive gastric cancer patients. Over the last decade, several groups have been working for deepening into the molecular characterization of gastric cancer, shedding some light into the heterogeneity of this tumour. The published data have broadened the landscape towards a future molecular classification into several subtypes of gastric cancer, enabling a better selection of the optimal therapeutic strategy. The fibroblast growth factor receptor (FGFR) pathway plays a key role in gastric cancer pathogenesis, with 1.2%-9% of gastric cancer patients harbouring FGFR2 amplifications. Several selective FGFR inhibitors have been developed in the last years, with promising efficacy signals. However, there is still scarce evidence of the most reliant molecular determinants of response to these targeted agents. Homogeneous high-level clonal FGFR2-amplification, high FGFR2 mRNA or protein levels, specific FGFR2 C3 isoform expression, FGF ligand co-overexpression or detection of FGFR2 copy number in plasma circulating tumour DNA, are considered some of the potential predictive biomarkers to the FGFR inhibition. The successful development of highly specific FGFR inhibitors will rely on our capacity of establishing new personalized strategies, based on a deeper knowledge of the key alterations that drive oncogenesis in gastric cancer. Further efforts seem mandatory in order to implement accurate predictive biomarkers in the next stages of the FGFR inhibitors development.
Original languageEnglish
Pages (from-to)1207-1216
JournalAnnals of Oncology
Volume28
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Fibroblast growth factor receptor
  • Fibroblast growth factor receptor inhibitors
  • Gastric cancer
  • Predictive biomarkers

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