Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition
Our findings point to intratumoral heterogeneity as a limiting factor in the use of DNA methyltransferase inhibitors as single agents in treatment of solid cancers and highlight histone deacetylase inhibitors as essential partners to DNA methyltransferase inhibitors in the clinic.
Authors
- Mikkel G. Terp (ORCID: https://orcid.org/0000-0002-4468-6900)
- Sofie Traynor (ORCID: https://orcid.org/0000-0003-2565-5110)
- Anup Shrestha (ORCID: https://orcid.org/0000-0003-3056-9575)
- Henrik J. Ditzel (ORCID: https://orcid.org/0000-0003-3927-5135)
- Aaraby Nielsen (ORCID: https://orcid.org/0000-0003-2199-2857)
- Christina Dahl (ORCID: https://orcid.org/0000-0002-6177-2640)
- Jonathan R. Brewer (ORCID: https://orcid.org/0000-0002-3444-1715)
- Maria S. Madsen (ORCID: https://orcid.org/0000-0002-5039-340X)
- Odd Lilleng Gammelgaard (ORCID: https://orcid.org/0000-0002-5911-7276)
- Mie K. Jakobsen (ORCID: https://orcid.org/0000-0001-7980-4623)
- Per Guldberg (ORCID: https://orcid.org/0000-0002-4424-4803)
- Josefine B. Jensen
- Mette Stæhr (ORCID: https://orcid.org/0000-0001-8680-4373)
- Pascal H. G. Duijf (ORCID: https://orcid.org/0000-0001-8646-9843)
- Simon T. Jakobsen (ORCID: https://orcid.org/0000-0002-6343-0660)
- Morten F. Gjerstorff (ORCID: https://orcid.org/0000-0002-0845-1952)
- Alexei F. Kirkin
- Rasmus Siersbæk (ORCID: https://orcid.org/0000-0002-8481-2182)
- Christina B. Pedersen (ORCID: https://orcid.org/0000-0002-9895-0930)
Institutions
- South Australia Pathology (AU)
- Oslo University Hospital (NO)
- University of South Australia (AU)
- University of Southern Denmark (DK)
- University of Oslo (NO)
- Odense University Hospital (DK)
- Centre for Cancer Biology (AU)
- Danish Cancer Society (DK)
- Danish Diabetes Academy (DK)
- Cytovac (Denmark) (DK)
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2025-01-23
- DOI
- https://doi.org/10.1186/s13046-025-03294-x
- Citations
- 7
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Dagmar Marshalls Fond
- Kræftens Bekæmpelse
- Villum Fonden
- Agnes og Poul Friis Fond
- Syddansk Universitet
- Frimodt-Heineke Fonden
- Novo Nordisk Fonden