Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance

Journal of Hematology & Oncology
Zhentao LiuLin Shen

Abstract

No approved targeted agents are available for esophageal squamous cell carcinoma (ESCC). Informative genomic analysis and mouse patient-derived xenografts (PDX) also called mouse avatar can greatly expedite drug discovery. Six ESCC cell lines and 7 out of 25 PDX models derived from 188 biopsies with clear molecular features were employed to evaluate the sensitivity of several EGFR blockers in vitro and in vivo, as well as the underlying antitumor mechanisms of the most promising EGFR-TKI afatinib. Mechanisms involved in acquired resistance of afatinib were explored based on established resistant cell lines and PDX models followed by an attempt to reverse resistance. Compared with other EGFR blockers, the second-generation EGFR-TKI afatinib exerted superior antitumor effects in ESCC, and EGFR copy number gain (CNG) or overexpression was proposed to be predictive biomarkers. Afatinib played its antitumor effects by inhibiting EGFR downstream pathways, as well as inducing apoptosis and cell cycle arrest at G1. It was increased phosphorylation of Src family kinases (SFKs), rather than MET upregulation, that conferred to acquired resistance of afatinib. Dual blockade of EGFR and SFKs could overcome afatinib resistance and warrants v...Continue Reading

References

Apr 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maarten L JanmaatGiuseppe Giaccone
Jun 3, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karen L ReckampRobert A Figlin
Sep 30, 2009·Nature Reviews. Clinical Oncology·Lori C KimEric B Haura
Mar 25, 2011·Science Translational Medicine·Lecia V SequistJeffrey A Engelman
Dec 14, 2011·Trends in Pharmacological Sciences·Siyuan Zhang, Dihua Yu
Feb 5, 2013·Lancet·Arjun PennathurJames D Luketich
Apr 2, 2014·Nature Genetics·De-Chen LinH Phillip Koeffler
Jun 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takeshi YoshidaEric B Haura
Aug 26, 2014·Nature Genetics·Yi-Bo GaoJie He
Dec 30, 2014·The New England Journal of Medicine·Anil K Rustgi, Hashem B El-Serag
Jul 18, 2015·World Journal of Gastroenterology : WJG·María José Domper ArnalÁngel Lanas Arbeloa
Mar 17, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Jing HuangYan Sun
May 14, 2017·Journal of Hematology & Oncology·Yunxin LaiPeng Li
May 26, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Russell D PettyZosia Miedzybrodzka
Oct 27, 2017·Nature Reviews. Cancer·Julia Rotow, Trever G Bivona

❮ Previous
Next ❯

Citations

Apr 19, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Adwitiya KarKatja Kiseljak-Vassiliades
Sep 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi ZhangFan-Hao Meng
Sep 4, 2020·Diagnostics·Anca OnaciuIoana Berindan-Neagoe
Mar 16, 2021·Journal of Gastroenterology and Hepatology·Li-Yan YangMing-Rong Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
genotyping
xenograft
PCR
flow cytometry
RNA-seq

Software Mentioned

ModFit LT
Copy Caller
ImageJ
SPSS
FlowJo
Graphpad

Related Concepts

Related Feeds

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

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.