Dataset Information

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

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.

SUBMITTER: Schmidt DR

PROVIDER: S-EPMC10412558 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Schmidt Daniel R DR Gramatikov Iva Monique T IMT Sheen Allison A Williams Christopher L CL Hurwitz Martina M Dodge Laura E LE Holupka Edward E Kiger W S WS Cornwall-Brady Milton R MR Huang Wei W Mak Howard H HH Cormier Kathleen S KS Condon Charlene C Dane Wittrup K K Yilmaz Ömer H ÖH Stevenson Mary Ann MA Down Julian D JD Floyd Scott R SR Roper Jatin J Vander Heiden Matthew G MG

Communications medicine 20230809 1

<h4>Background</h4>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.<h4>Methods</h4>Here we report the development, testing, and validation of a ...[more]

PMID: 37558833

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Project description:Prostate is the most common non-cutaneous cancer diagnosed among men in North America. Fortunately most prostate cancers are screen detected and non-metastatic on diagnosis. Treatment options for men with localized prostate cancer include surgery ± postoperative radiation or radiation ± androgen deprivation therapy (ADT). Brachytherapy ± external beam radiation treatment (EBRT) appears to have superior long-term disease control over EBRT alone likely because of higher biologic effective dose delivered. Stereotactic ablative body radiation (SABR) is a novel, non-invasive, high-precision EBRT technique that allows safe delivery of biologic doses similar to brachytherapy with similar or lower side effects [measured using toxicity or quality of life (QOL) scales]. Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2-3 years post treatment, biochemical failure (BF) rates out to 10-year and incidence of metastases. SABR dose escalation reduces biopsy positivity and prostate-specific antigen (PSA) nadirs but increases genitourinary (GU) and gastrointestinal (GI) toxicity-no effect on BF has been realized yet. The overall treatment time (OTT) varies in many protocols. Phase 2 randomized data shows that QOL is better in the acute setting with a weekly course of treatment compared to an every other day treatment regimen with no difference in late setting. Follow-up data are immature and likely underpowered to determine efficacy differences. SABR is cheaper and uses less resource than any other radiation technique. Given the healthcare resource challenges (including financial resources), SABR would be a welcomed addition if studies show non-inferiority to other radiation techniques. For patients with de novo or metastatic disease on relapse, there is much enthusiasm regarding the use of SABR in the setting of oligometastatic prostate cancer. SABR appears to be feasible to deliver, well tolerated and may delay the next line of therapy. However, until adequately powered randomized studies confirm a benefit, such an approach cannot be considered standard of care treatment at this time. Enrollment of eligible prostate cancer patients onto SABR clinical trials should be encouraged.

Dataset Information

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Background

Methods

Results

Conclusions

Publications

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Similar Datasets

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