Impact of hypofractionated radiotherapy on 3D breast cancer models
A hypofractionated radiation therapy (RT) regimen delivering 5.2 Gy per fraction (total 26 Gy) is safe and effective, providing breast cancer (BCa) control for up to five years. However, there is limited knowledge about cellular responses to hypofractionated RT using relevant preclinical models. In this study, three-dimensional (3D) gelatin methacryloyl (GelMA) hydrogels were utilized to examine BCa cell response to hypofractionated RT. Herein, 3D cultures of MCF-7 and MDA-MB-231 cell lines and patient-derived BCa cells were subjected to hypofractionated RT and grown over 70 days in GelMA hydrogels. To assess the cellular response, we analyzed metabolic activity, DNA damage, cell viability and molecular markers of cancer stem cells (CSCs). Cell viability and metabolic activity declined following RT in both BCa cell lines and patient-derived cells. RT significantly increased CSC marker ALDH1A1 by day 35. Post-RT, CSC subpopulations secreted IL-8, potentially associated with an increase in tumor aggressiveness. This study demonstrates BCa cell responses to hypofractionated RT and highlights GelMA as a valuable preclinical RT model.
Authors
- Julien Clegg (ORCID: https://orcid.org/0000-0002-4250-2856)
- Nanthini Jayabalan (ORCID: https://orcid.org/0000-0002-9669-9367)
- Lucy Sim (ORCID: https://orcid.org/0000-0001-7251-3567)
- Larisa M. Haupt (ORCID: https://orcid.org/0000-0002-7735-8110)
- Akhilandeshwari Ravichandran (ORCID: https://orcid.org/0000-0003-4807-1150)
- Andrew L. Fielding (ORCID: https://orcid.org/0000-0001-9955-4609)
- F Sofia Hilmi (ORCID: https://orcid.org/0000-0002-3626-1857)
- Mikaela Westlake
- Mark N. Adams
- Tom van de Kemp (ORCID: https://orcid.org/0009-0008-8626-0386)
- Laura J. Bray (ORCID: https://orcid.org/0000-0002-1174-0018)
- Gishan Ratnayake (ORCID: https://orcid.org/0000-0003-4320-3601)
- Son H. Pham (ORCID: https://orcid.org/0000-0002-3862-9336)
- Lachlan Barnard (ORCID: https://orcid.org/0009-0002-0067-8439)
- Shiva Taheri (ORCID: https://orcid.org/0000-0001-8346-668X)
Institutions
- Queensland University of Technology (AU)
- The Alfred Hospital (AU)
- Metro South Health (AU)
- Applied Tissue Technologies (United States) (US)
- Alfred Health (AU)
- Monash University (AU)
Publication Details
- Journal
- Materials Today Advances
- Published
- 2026-05-27
- DOI
- https://doi.org/10.1016/j.mtadv.2026.100827
- Primary Topic
- Advanced Radiotherapy Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Breast Cancer Foundation
- Australian Research Council