Imperial College London
Alternate

DrChiaraRecchi

Faculty of Medicine, Department of Surgery & Cancer

Honorary Senior Lecturer
 
 
 
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Contact

 

c.recchi

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zanini:2017:10.1158/1535-7163.MCT-17-0081,
author = {Zanini, E and Louis, LS and Antony, J and Karali, E and Okon, IS and McKie, AB and Vaughan, S and El-Bahrawy, M and Stebbing, J and Recchi, C and Gabra, H},
doi = {10.1158/1535-7163.MCT-17-0081},
journal = {Molecular Cancer Therapeutics},
pages = {2246--2256},
title = {The tumor suppressor protein OPCML potentiates anti-EGFR and anti-HER2 targeted therapy in HER2-positive ovarian and breast cancer.},
url = {http://dx.doi.org/10.1158/1535-7163.MCT-17-0081},
volume = {16},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OPCML is a tumor suppressor gene that is frequently inactivated in ovarian cancer and many other cancers by somatic methylation. We have previously shown that OPCML exerts its suppressor function by negatively regulating a spectrum of receptor tyrosine kinases (RTKs), such as ErbB2/HER2, FGFR1 and EphA2, thus attenuating their related downstream signaling. The physical interaction of OPCML with this defined group of RTKs is a prerequisite for their downregulation. Overexpression/gene amplification of EGFR and HER2 is a frequent event in multiple cancers including ovarian and breast cancers. Molecular therapeutics against EGFR/HER2 or EGFR only, such as lapatinib and erlotinib respectively, were developed to target these receptors but resistance often occurs in relapsing cancers. Here we show that, though OPCML interacts only with HER2 and not with EGFR, the interaction of OPCML with HER2 disrupts the formation of the HER2-EGFR heterodimer and this translates into a better response to both lapatinib and erlotinib in HER2-expressing ovarian and breast cancer cell lines. Also, we show that high OPCML expression is associated with better response to lapatinib therapy in breast cancer patients and better survival in HER2-overexpressing ovarian cancer patients, suggesting that OPCML co-therapy could be a valuable sensitizing approach to RTK inhibitors.
AU  - Zanini,E
AU  - Louis,LS
AU  - Antony,J
AU  - Karali,E
AU  - Okon,IS
AU  - McKie,AB
AU  - Vaughan,S
AU  - El-Bahrawy,M
AU  - Stebbing,J
AU  - Recchi,C
AU  - Gabra,H
DO  - 10.1158/1535-7163.MCT-17-0081
EP  - 2256
PY  - 2017///
SN  - 1535-7163
SP  - 2246
TI  - The tumor suppressor protein OPCML potentiates anti-EGFR and anti-HER2 targeted therapy in HER2-positive ovarian and breast cancer.
T2  - Molecular Cancer Therapeutics
UR  - http://dx.doi.org/10.1158/1535-7163.MCT-17-0081
UR  - http://hdl.handle.net/10044/1/50126
VL  - 16
ER  -
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