Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2-Amplified Gastric Cancer Patient-Derived Cell Model

Translational Oncology
Jiryeon JangKyoung-Mee Kim

Abstract

FGFR2 amplification is associated with aggressive gastric cancer (GC), and targeted drugs have been developed for treatment of GC. We evaluated the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with peritoneal carcinomatosis. Two GC patients with FGFR2 amplification confirmed by fluorescence in situ hybridization showed peritoneal seeding and malignant ascites. We used the patient-derived xenograft model; patient-derived cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its downstream pathway using immunofluorescence analysis and immunoblot assay in vitro. Apoptosis and cell cycle arrest after treatment of FGFR inhibitor were analyzed by Annexin V-FITC assay and cell cycle analysis. FGFR2 amplification was verified in both PDC lines. AZD4547 as an FGFR inhibitor decreased proliferation of PDCs, and the IC50 value was estimated to be 250 nM in PDC#1 and 210 nM in PDC#2. FGFR inhibitor also significantly decreased levels of phosphorylated FGFR2 and downstream signaling molecules in FGFR2-amplified PDC lines. In cell cycle analysis, apoptosis was significantly increased in AZD4547-treated cells compared with nontreated cells. The proportion of cells in the sub-G1 stage was signif...Continue Reading

References

Sep 6, 2005·Cancer Research·Helen DaviesP Andrew Futreal
Jul 23, 2016·Oncotarget·Matias RiihimäkiKari Hemminki

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Citations

Jun 26, 2018·Expert Review of Anticancer Therapy·Gaia Cristina GhediniArianna Giacomini
Oct 28, 2018·Nature Reviews. Clinical Oncology·Masaru Katoh
Jun 28, 2019·Cells·Jinglin ZhangKa Fai To
May 22, 2020·Investigational New Drugs·Nikki PhanhthilathPeter E Zage
Aug 17, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Akira Ooki, Kensei Yamaguchi
Aug 12, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tomoko JogoTakayuki Yoshino
Nov 25, 2021·Expert Opinion on Emerging Drugs·Maria AlsinaJosep Tabernero

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Methods Mentioned

BETA
Reverse Transcription Polymerase Chain Reaction
PCR
biopsy
flow cytometry
xenograft

Clinical Trials Mentioned

NCT01457846

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis