Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer
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Published version
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Author(s)
Schmidt, Daniel R
Gramatikov, Iva Monique T
Sheen, Allison
Williams, Christopher L
Hurwitz, Martina
Dodge, Laura E
Holupka, Edward
Kiger, WS
Cornwall-Brady, Milton R
Huang, Wei
Date Issued
August 9, 2023
Journal
Communications Medicine
Publisher
Springer Science and Business Media LLC
Citation
Schmidt, D.R., Gramatikov, I.M.T., Sheen, A. et al. Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer. Commun Med 3, 108 (2023).
Version
Final published version
Abstract
Background
Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation therapy (RT) is frequently used to treat localized cancers with curative intent, delay progression of oligometastases, and palliate symptoms of metastatic disease.
Methods
Here we report the development, testing, and validation of a platform to immobilize and target tumors in mice with stereotactic ablative RT (SART). Xenograft and autochthonous tumor models were treated with hypofractionated ablative doses of radiotherapy.
Results
We demonstrate that hypofractionated regimens used in clinical practice can be effectively delivered in mouse models. SART alters tumor stroma and the immune environment, improves survival in GEMMs of primary prostate and colorectal cancer, and synergizes with androgen deprivation in prostate cancer. Complete pathologic responses were achieved in xenograft models, but not in GEMMs.
Conclusions
While SART is capable of fully ablating xenografts, it is unable to completely eradicate disease in GEMMs, arguing that resistance to potentially curative therapy can be modeled in GEMMs.
Plain language summary
Mice can be used to model the types of cancer seen in people to investigate the effects of cancer therapies, such as radiation. Here, we apply radiation therapy treatments that are able to cure cancer in humans to mice that have cancer of the prostate or colorectum. We show that the mice do not experience many side effects and that the tumours reduce in size, but in some cases show progression after treatment. Our study demonstrates that mice can be used to better understand how human cancers respond to radiation treatment, which can lead to the development of improved treatments and treatment schedules.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
10.1038/s43856-023-00336-3
