Merging perspectives: genotype-directed molecular therapy for hereditary diffuse gastric cancer (HDGC) and E-cadherin-EGFR crosstalk

Clinical and Translational Medicine
Dandan LiUdo Rudloff

Abstract

Hereditary diffuse gastric cancer is a cancer predisposition syndrome associated with germline mutations of the E-cadherin gene (CDH1; NM_004360). Male CDH1 germline mutation carriers have by the age of 80 years an estimated 70% cumulative incidence of gastric cancer, females of 56% for gastric and of 42% for lobular breast cancer. Metastatic HDGC has a poor prognosis which is worse than for sporadic gastric cancer. To date, there have been no treatment options described tailored to this molecular subtype of gastric cancer. Here we review recent differential drug screening and gene expression results in c.1380del CDH1-mutant HDGC cells which identified drug classes targeting PI3K (phosphoinositide 3-kinase), MEK (mitogen-activated protein kinase), FAK (focal adhesion kinase), PKC (protein kinase C), and TOPO2 (topoisomerase II) as selectively more effective in cells with defective CDH1 function. ERK1-ERK2 (extracellular signal regulated kinase) signaling measured as top enriched network in c.1380delA CDH1-mutant cells. We compared these findings to synthetic lethality and pharmacological screening results in isogenic CDH1-/- MCF10A mammary epithelial cells with and without CDH1 expression and current knowledge of E-cadherin/cat...Continue Reading

References

May 16, 1998·The Journal of Biological Chemistry·R B Hazan, L Norton
Dec 14, 1999·The Journal of Biological Chemistry·S RouraM Duñach
Dec 1, 2001·Gastroenterology·P D PharoahUNKNOWN International Gastric Cancer Linkage Consortium
Jan 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sarah E Seton-RogersJoan S Brugge
Aug 16, 2005·Current Opinion in Cell Biology·Jack Lilien, Janne Balsamo
Dec 13, 2006·Future Oncology·Amber YasmeenAla-Eddin Al Moustafa
May 19, 2007·Human Molecular Genetics·Ana Rita MateusBirgit Luber
Jun 5, 2007·JAMA : the Journal of the American Medical Association·Pardeep KaurahDavid Huntsman
Mar 10, 2009·Experimental Cell Research·Ana Rita MateusRaquel Seruca
Aug 21, 2010·The American Journal of Pathology·I-Rue LaiTang-Long Shen
Dec 14, 2011·Trends in Pharmacological Sciences·Siyuan Zhang, Dihua Yu
Nov 6, 2012·International Journal of Cancer. Journal International Du Cancer·Patrick R BenusiglioDavid Malka
Jan 24, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giovanni CorsoCarla Oliveira
May 28, 2013·Journal of Medical Genetics·Patrick R BenusiglioOlivier Caron
May 17, 2015·Journal of Medical Genetics·Rachel S van der PostRebecca C Fitzgerald
Jul 17, 2015·JAMA Oncology·Samantha HansfordDavid G Huntsman

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Citations

May 14, 2019·Journal of Cellular Biochemistry·Jianwei LiJianguo Sun
Sep 5, 2020·Molecular Genetics & Genomic Medicine·Carmen Martínez ValenzuelaAna Laura Calderón-Garcidueñas
Feb 13, 2020·International Journal of Molecular Sciences·Davide AngeliGianluca Tedaldi
Jul 15, 2018·Journal of Cellular and Molecular Medicine·Beibei ChenXiao-Bing Chen
Jun 11, 2021·Oncogene·Kara M McNamaraKeith T Wilson

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Methods Mentioned

BETA
nuclear translocation

Software Mentioned

MetaCore

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