APOBEC3 mutagenesis drives therapy resistance in breast cancer Article Swipe
Avantika Gupta
,
Andrea Gazzo
,
Pier Selenica
,
Anton Safonov
,
Fresia Pareja
,
Edaise M. da Silva
,
David N. Brown
,
Hong Shao
,
Yingjie Zhu
,
Juber Patel
,
Juan Blanco-Heredia
,
Bojana Stefanovska
,
Michael A. Carpenter
,
Yanjun Chen
,
Isabella Vegas
,
Xin Pei
,
Denise Frosina
,
Achim A. Jungbluth
,
Marc Ladanyi
,
Giuseppe Curigliano
,
Britta Weigelt
,
Nadeem Riaz
,
Simon N. Powell
,
Pedram Razavi
,
Reuben S. Harris
,
Jorge S. Reis‐Filho
,
Antonio Marra
,
Sarat Chandarlapaty
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41588-025-02187-1
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41588-025-02187-1
Acquired genetic alterations drive resistance to endocrine and targeted therapies in metastatic breast cancer; however, the underlying processes engendering these alterations are largely uncharacterized. To identify the underlying mutational processes, we utilized a clinically annotated cohort of 3,880 patient samples with tumor-normal sequencing. Mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were prevalent and enriched in post-treatment hormone receptor-positive cancers. These signatures correlated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor therapy in hormone receptor-positive metastatic breast cancer. Whole-genome sequencing of breast cancer models and paired primary-metastatic samples demonstrated that active APOBEC3 mutagenesis promoted therapy resistance through characteristic alterations such as RB1 loss. Evidence of APOBEC3 activity in pretreatment samples illustrated its pervasive role in breast cancer evolution. These studies reveal APOBEC3 mutagenesis to be a frequent mediator of therapy resistance in breast cancer and highlight its potential as a biomarker and target for overcoming resistance.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41588-025-02187-1
- https://www.nature.com/articles/s41588-025-02187-1.pdf
- OA Status
- hybrid
- Cited By
- 6
- References
- 91
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410447694
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410447694Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41588-025-02187-1Digital Object Identifier
- Title
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APOBEC3 mutagenesis drives therapy resistance in breast cancerWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-05-16Full publication date if available
- Authors
-
Avantika Gupta, Andrea Gazzo, Pier Selenica, Anton Safonov, Fresia Pareja, Edaise M. da Silva, David N. Brown, Hong Shao, Yingjie Zhu, Juber Patel, Juan Blanco-Heredia, Bojana Stefanovska, Michael A. Carpenter, Yanjun Chen, Isabella Vegas, Xin Pei, Denise Frosina, Achim A. Jungbluth, Marc Ladanyi, Giuseppe Curigliano, Britta Weigelt, Nadeem Riaz, Simon N. Powell, Pedram Razavi, Reuben S. Harris, Jorge S. Reis‐Filho, Antonio Marra, Sarat ChandarlapatyList of authors in order
- Landing page
-
https://doi.org/10.1038/s41588-025-02187-1Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41588-025-02187-1.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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https://www.nature.com/articles/s41588-025-02187-1.pdfDirect OA link when available
- Concepts
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Biology, Mutagenesis, Breast cancer, Genetics, Cancer research, Cancer, Mutation, Computational biology, Bioinformatics, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
6Total citation count in OpenAlex
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2025: 6Per-year citation counts (last 5 years)
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91Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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