Reduction of Global H3K27me Enhances HER2/ErbB2 Targeted Therapy.

Clicks: 381
ID: 59221
2019
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #13 of 65 articles by views in Cell reports

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibit de novo resistance. Here, by comparing matched Trastuzumab-naive and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me, a repressive histone modification catalyzed by polycomb repressor complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor type-I interferon (IFN) responses. In patients, elevated H3K27me in tumor cells following Trastuzumab treatment correlates with suppression of interferon-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote interferon-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me depletion in Trastuzumab-resistant disease.
Reference Key
hirukawa2019reductioncell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hirukawa, Alison;Singh, Salendra;Wang, Jarey;Rennhack, Jonathan P;Swiatnicki, Matthew;Sanguin-Gendreau, Virginie;Zuo, Dongmei;Daldoul, Kamilia;Lavoie, Cynthia;Park, Morag;Andrechek, Eran R;Westbrook, Thomas F;Harris, Lyndsay N;Varadan, Vinay;Smith, Harvey W;Muller, William J;
Journal Cell reports
Year 2019
DOI
S2211-1247(19)31167-2
URL
Keywords
Breast cancer epigenetics transcriptional silencing erbb2/her2 prc2 polycomb repressor complex 2 trastuzumab resistance endogenous retroviruses immune surveillance type i interferon signaling

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.