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Simultaneous Inhibition of Estrogen Receptor and the HER2 Pathway in Breast Cancer: Effects of HER2 Abundance.

Anna Emde Georg Mahlknecht Kerstin Maslak Benjamin Ribba 1 Michael Sela Kurt Possinger 2 Yosef Yarden 
1 NUMED - Numerical Medicine
UMPA-ENSL - Unité de Mathématiques Pures et Appliquées, Inria Grenoble - Rhône-Alpes
Abstract : The estrogen receptor (ER) pathway and the epidermal growth factor receptor (EGFR) pathway play pivotal roles in breast cancer progression. Targeted therapies able to intercept ER or signaling downstream to EGFR and its kin, HER2, are routinely used to treat distinct groups of breast cancer patients. However, patient responses are limited by resistance to endocrine therapy, which may be due to compensatory HER2/EGFR signaling. This raises the possibility that simultaneous interception of HER2 and ER may enhance therapeutic efficacy. To address the question, we treated breast cancer cells with both fulvestrant (ICI 182780), an ER antagonist with no agonist effects, and lapatinib, an orally available tyrosine kinase inhibitor specific to EGFR and HER2. Our results indicate that the combination of drugs is especially effective when applied to HER2-overexpressing, ER-positive cancer cells. Interestingly, fulvestrant activated the mitogen-activated protein kinase (MAPK) pathway of these cells, but complete inhibition of MAPK signaling was observed on cotreatment with lapatinib. Taken together, our observations reinforce the possibility that the effectiveness of combining anti-ER and anti-HER2/EGFR drugs may be especially effective on a relatively small subtype of HER2-overexpressing, ER-positive tumors of the breast.
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Contributor : Benjamin Ribba Connect in order to contact the contributor
Submitted on : Thursday, November 22, 2012 - 7:14:52 PM
Last modification on : Wednesday, March 9, 2022 - 3:30:41 PM


  • HAL Id : hal-00756353, version 1
  • PUBMED : 21966546



Anna Emde, Georg Mahlknecht, Kerstin Maslak, Benjamin Ribba, Michael Sela, et al.. Simultaneous Inhibition of Estrogen Receptor and the HER2 Pathway in Breast Cancer: Effects of HER2 Abundance.. Translational Oncology, 2011, 4 (5), pp.293-300. ⟨hal-00756353⟩



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