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Mechanism of Endocrine Therapy Resistance in Breast Cancer: New Insights and Implications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (25 March 2019) | Viewed by 6093

Special Issue Editors

Inserm U1052, Centre de Recherche en Cancérologie de Lyon (CRCL), Lyon, France
Interests: breast cancer; estrogen receptor; progesterone receptor; cell signaling; arginine methylation; arginine demethylation; post translational modifications; transcriptional regulation
Special Issues, Collections and Topics in MDPI journals
Institut Curie, PSL Research University, Translational Research Department, 75005 Paris, France
Interests: predictive biomarkers in PDX; PI3K and endocrine therapies; drug combinations; PDX

Special Issue Information

Dear Colleagues,

Estrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies targeting the estrogen receptor activity have largely improved patient survival. However, the development of resistance has led to identify drivers of this phenomenom, such as mTOR inhibitors and inhibitors of cyclin-dependent kinases CDK4 and CDK6. However, new targeted therapies are being developed in order to offer more therapeutical options, and to circumvent the problem of resistance.

This Special Issue welcomes submissions of research articles and reviews covering all aspects of endocrine therapies in breast cancer, from the basic science to the clinical trials. There will be special focus on new promising drugs as well as on potential biomarkers that are predictive for a therapeutic response.

Dr. Muriel Le Romancer
Dr. Elisabetta Marangoni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • breast cancer
  • estrogen
  • estrogen receptors
  • cell signaling
  • protein kinases
  • targeted therapy
  • resistance
  • biomarkers

Published Papers (2 papers)

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Research

13 pages, 3775 KiB  
Article
Oestrogen Non-Genomic Signalling is Activated in Tamoxifen-Resistant Breast Cancer
by Coralie Poulard, Julien Jacquemetton, Olivier Trédan, Pascale A. Cohen, Julie Vendrell, Sandra E. Ghayad, Isabelle Treilleux, Elisabetta Marangoni and Muriel Le Romancer
Int. J. Mol. Sci. 2019, 20(11), 2773; https://doi.org/10.3390/ijms20112773 - 05 Jun 2019
Cited by 13 | Viewed by 2909
Abstract
Endocrine therapies targeting oestrogen signalling have significantly improved breast cancer management. However, their efficacy is limited by intrinsic and acquired resistance to treatment, which remains a major challenge for oestrogen receptor α (ERα)-positive tumours. Though many studies using in vitro models of endocrine [...] Read more.
Endocrine therapies targeting oestrogen signalling have significantly improved breast cancer management. However, their efficacy is limited by intrinsic and acquired resistance to treatment, which remains a major challenge for oestrogen receptor α (ERα)-positive tumours. Though many studies using in vitro models of endocrine resistance have identified putative actors of resistance, no consensus has been reached. We demonstrated previously that oestrogen non-genomic signalling, characterized by the formation of the ERα/Src/PI3K complex, is activated in aggressive breast cancers (BC). We wondered herein whether the activation of this pathway is also involved in resistance to endocrine therapies. We studied the interactions between ERα and Src or PI3K by proximity ligation assay (PLA) in in-vitro and in-vivo endocrine therapy-resistant breast cancer models. We reveal an increase in ERα/Src and ERα/PI3K interactions in patient-derived xenografts (PDXs) with acquired resistance to tamoxifen, as well as in tamoxifen-resistant MCF-7 cells compared to parental counterparts. Moreover, no interactions were observed in breast cancer cells resistant to other endocrine therapies. Finally, the use of a peptide inhibiting the ERα–Src interaction partially restored tamoxifen sensitivity in resistant cells, suggesting that such components could constitute promising targets to circumvent resistance to tamoxifen in BC. Full article
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15 pages, 1916 KiB  
Article
Dual Epigenetic Regulation of ERα36 Expression in Breast Cancer Cells
by Charlène Thiebaut, Amand Chesnel, Jean-Louis Merlin, Maelle Chesnel, Agnès Leroux, Alexandre Harlé and Hélène Dumond
Int. J. Mol. Sci. 2019, 20(11), 2637; https://doi.org/10.3390/ijms20112637 - 29 May 2019
Cited by 13 | Viewed by 2805
Abstract
Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ERα36 was reported to play a crucial role [...] Read more.
Breast cancer remains the major cause of cancer-induced morbidity and mortality in women. Among the different molecular subtypes, luminal tumors yet considered of good prognosis often develop acquired resistance to endocrine therapy. Recently, misregulation of ERα36 was reported to play a crucial role in this process. High expression of this ERα isoform was associated to preneoplastic phenotype in mammary epithelial cells, disease progression, and enhanced resistance to therapeutic agents in breast tumors. In this study, we identified two mechanisms that could together contribute to ERα36 expression regulation. We first focused on hsa-miR-136-5p, an ERα36 3’UTR-targeting microRNA, the expression of which inversely correlated to the ERα36 one in breast cancer cells. Transfection of hsa-miR136-5p mimic in MCF-7 cells resulted in downregulation of ERα36. Moreover, the demethylating agent decitabine was able to stimulate hsa-miR-136-5p endogenous expression, thus indirectly decreasing ERα36 expression and counteracting tamoxifen-dependent stimulation. The methylation status of ERα36 promoter also directly modulated its expression level, as demonstrated after decitabine treatment of breast cancer cell and confirmed in a set of tumor samples. Taken together, these results open the way to a direct and an indirect ERα36 epigenetic modulation by decitabine as a promising clinical strategy to counteract acquired resistance to treatment and prevent relapse. Full article
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