The EstroGene2.0 database for endocrine therapy response and resistance in breast cancer
Endocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities ( https://estrogeneii.web.app/ ). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed transcriptomic landscape and substantial diversity in response to different classes of ER modulators. Endocrine-resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signalings, which is recapitulated clinically. Dissecting multiple ESR1-mutant cell models revealed the different clinical relevance of cell model engineering and identified high-confidence mutant-ER targets, such as NPY1R. These examples demonstrate how EstroGene2.0 helps investigate breast cancer's response to endocrine therapies and explore resistance mechanisms.
Authors
- Steffi Oesterreich (ORCID: https://orcid.org/0000-0002-2537-6923)
- Matthew J. Sikora (ORCID: https://orcid.org/0000-0003-2915-7442)
- Joanna Kirkpatrick (ORCID: https://orcid.org/0000-0001-9291-7294)
- Kornélia Polyák (ORCID: https://orcid.org/0000-0002-5964-0382)
- Fazal Hadi (ORCID: https://orcid.org/0000-0003-3553-817X)
- Jason Gertz (ORCID: https://orcid.org/0000-0001-7568-6789)
- Soleilmane Omarjee (ORCID: https://orcid.org/0000-0001-8686-7286)
- Adrian V. Lee (ORCID: https://orcid.org/0000-0001-9917-514X)
- Kamal Kishore (ORCID: https://orcid.org/0000-0002-4650-8745)
- Fangyuan Chen (ORCID: https://orcid.org/0000-0002-9891-4753)
- Mandy Lawson (ORCID: https://orcid.org/0009-0002-0781-8393)
- Zheqi Li (ORCID: https://orcid.org/0000-0003-1213-640X)
- Jiebin Liu
- Jason S. Carroll (ORCID: https://orcid.org/0000-0003-3643-0080)
- Li Chen (ORCID: https://orcid.org/0000-0003-0977-2384)
- Clive S. D’Santos (ORCID: https://orcid.org/0000-0003-4592-0487)
- Joshua Kent
- Danielle Tseng
- Donald P. McDonnell
Institutions
- AstraZeneca (United Kingdom) (GB)
- Harvard University (US)
- University of Pittsburgh (US)
- Duke University (US)
- University of Utah (US)
- University of Cambridge (GB)
- Cancer Research UK (GB)
- UPMC Health System (US)
- Dana-Farber Cancer Institute (US)
- Cancer Research Center (US)
- UPMC Hillman Cancer Center (US)
- University of Pittsburgh Medical Center (US)
- University of Colorado Anschutz Medical Campus (US)
- Carnegie Mellon University (US)
- Tsinghua University (CN)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1038/s41523-024-00709-4
- Citations
- 2
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 0.57
Funders
- Breast Cancer Research Foundation
- AstraZeneca
- University of Pittsburgh
- Susan G. Komen
- Shear Family Foundation
- Cancer Research UK
- University of Cambridge
- Tsinghua University
- China Scholarship Council
- Hutchison Whampoa Limited
- National Institutes of Health
- Center for Research Computing, University of Pittsburgh
- National Cancer Institute