Estrogen Receptor Coregulator Binding Modulators (ERXs) Effectively Target Estrogen Receptor Positive Human Breast Cancers

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Estrogen Receptor Coregulator Binding Modulators (ERXs) Effectively Target Estrogen Receptor Positive Human Breast Cancers

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Title: Estrogen Receptor Coregulator Binding Modulators (ERXs) Effectively Target Estrogen Receptor Positive Human Breast Cancers
Author(s):
Raj, Ganesh V.;
Sareddy, Gangadhara Reddy;
Ma, Shihong;
Lee, Tae-Kyung;
Viswanadhapalli, Suryavathi;
Li, Rui;
Liu, Xihui;
Murakami, Shino;
Chen, Chien-Cheng;
Lee, Wan-Ru;
Mann, Monica;
Krishnan, Samaya Rajeshwari;
Manandhar, Bikash;
Gonugunta, Vijay K.;
Strand, Douglas;
Tekmal, Rajeshwar Rao;
Ahn, Jung-Mo;
Vadlamudi, Ratna K.
Date Created: 2017-08-08
Item Type: article
Keywords: Show Keywords
Abstract: The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.
ISSN: 2050-084X
Source: eLife
Link to Related Resource: http://dx.doi.org/10.7554/eLife.26857
Persistent Link: http://hdl.handle.net/10735.1/6113
Bibliographic Citation: Raj, Ganesh V., Gangadhara Reddy Sareddy, Shihong Ma, Tae-Kyung Lee, et al. 2017. "Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers." eLife 6, doi:10.7554/eLife.26857
Terms of Use: CC BY 4.0 (Attribution)
©2017 The Authors
Sponsors: Cancer Prevention and Research Institute of Texas grant no. DP150096; Congressionally Directed Medical Research Programs grant no. W81XWH-12-1-0288, W81XWH-13-2-0093, W81XWH-16-1-0294; CPRIT grant # DP150096; DOD grant # W81XWH-12-1- 0288 and W81XWH-13-2-0093; Welch Foundation (AT-1595); UTH Cancer Center grant P30 CA-54174; NIH grant 1R01CA179120-01.

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CC BY 4.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 4.0 (Attribution)