Patient-derived organoid xenografts reveal the multifaceted role of the lncRNA <i>MALAT1</i> in breast cancer progression
Background: is overexpressed in more than 20 cancers, including breast cancer and has been shown to function via various mechanisms in a context-dependent manner, in 2D cell lines and mouse models. However, its functional role and therapeutic potential have not been evaluated in clinically relevant patient-derived models. Methods: to study its impact on transcription, alternative splicing, stromal remodeling and metastasis. Results: depletion induced a consistent reduction in macrophage-associated gene signatures and reduced lung metastatic burden. Conclusions: -targeted ASO therapy and establishes PDO-X models as a clinically relevant platform for functional interrogation of TNBC therapies.
Authors
- Taylor Floyd
- Alexey S. Revenko (ORCID: https://orcid.org/0000-0002-4863-362X)
- Disha Aggarwal (ORCID: https://orcid.org/0000-0002-5374-8165)
- John Erby Wilkinson (ORCID: https://orcid.org/0000-0001-9174-8556)
- Qing Gao (ORCID: https://orcid.org/0000-0002-2029-0071)
- Kendall Anderson (ORCID: https://orcid.org/0000-0001-6519-0675)
- Sonam Bhatia (ORCID: https://orcid.org/0000-0002-0124-2621)
- Gayatri Arun (ORCID: https://orcid.org/0000-0002-7261-5296)
- Shuchismita R. Satpathy
- W. Richard McCombie (ORCID: https://orcid.org/0000-0003-1899-0682)
- Shruti V. Iyer (ORCID: https://orcid.org/0000-0002-4351-9975)
- David L. Spector (ORCID: https://orcid.org/0000-0003-3614-4965)
- Karen Kostroff
- Martin Akerman (ORCID: https://orcid.org/0000-0003-4457-1166)
- Melissa Kramer
- Payal Naik
- Raditya Utama
- Sara A Pawlak
- Suzanne Russo
- James A. Rouse
Institutions
- Northwell Health (US)
- Long Island University (US)
- Cold Spring Harbor Laboratory (US)
- Ionis Pharmaceuticals (United States) (US)
- Stony Brook University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-03
- DOI
- https://doi.org/10.64898/2026.04.02.716096
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cold Spring Harbor Laboratory
- Northwell Health
- National Institutes of Health
- National Cancer Institute