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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Added by mollevi
Last modified by pmartino
Group name EquipePM
Item Type Journal Article
Title HER3 as biomarker and therapeutic target in pancreatic cancer: new insights in pertuzumab therapy in preclinical models
Creator Thomas et al.
Author G. Thomas
Author T. Chardes
Author N. Gaborit
Author C. Mollevi
Author W. Leconet
Author B. Robert
Author N. Radosevic-Robin
Author F. Penault-Llorca
Author C. Gongora
Author P. E. Colombo
Author Y. Lazrek
Author R. Bras-Goncalves
Author A. Savina
Author D. Azria
Author H. Bazin
Author A. Pelegrin
Author C. Larbouret
Abstract The anti-HER2 antibody pertuzumab inhibits HER2 dimerization and affects HER2/HER3 dimer formation and signaling. As HER3 and its ligand neuregulin are implicated in pancreatic tumorigenesis, we investigated whether HER3 expression could be a predictive biomarker of pertuzumab efficacy in HER2low-expressing pancreatic cancer. We correlated in vitro and in vivo HER3 expression and neuregulin dependency with the inhibitory effect of pertuzumab on cell viability and tumor progression. HER3 knockdown in BxPC-3 cells led to resistance to pertuzumab therapy. Pertuzumab treatment of HER3-expressing pancreatic cancer cells increased HER3 at the cell membrane, whereas the anti-HER3 monoclonal antibody 9F7-F11 down-regulated it. Both antibodies blocked HER3 and AKT phosphorylation and inhibited HER2/HER3 heterodimerization but affected differently HER2 and HER3 homodimers. The pertuzumab/9F7-F11 combination enhanced tumor inhibition and the median survival time in mice xenografted with HER3-expressing pancreatic cancer cells. Finally, HER2 and HER3 were co-expressed in 11% and HER3 alone in 27% of the 45 pancreatic ductal adenocarcinomas analyzed by immunohistochemistry. HER3 is essential for pertuzumab efficacy in HER2low-expressing pancreatic cancer and HER3 expression might be a predictive biomarker of pertuzumab efficacy in such cancers. Further studies in clinical samples are required to confirm these findings and the interest of combining anti-HER2 and anti-HER3 therapeutic antibodies.
Publication Oncotarget
Volume 5
Pages 7138-48
Date Aug 30 2014
Journal Abbr Oncotarget
ISSN 1949-2553 (Electronic) 1949-2553 (Linking)
Tags Animals, Antibodies, Monoclonal, Humanized/*pharmacology, Antineoplastic Agents/*pharmacology, Cell Proliferation/drug effects, Female, Humans, mabimprove, Mice, Mice, Nude, original, Pancreatic Neoplasms/*drug therapy/*enzymology/pathology, Random Allocation, Receptor, ErbB-3/antagonists & inhibitors/*metabolism, rio, Signal Transduction, siric, Tumor Markers, Biological, Xenograft Model Antitumor Assays
Date Added 2018/07/20 - 09:15:34
Date Modified 2019/05/14 - 13:56:00
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25216528 (Attachment)


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