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Updated: Jun 6, 2026
An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis
Published on: August 14, 2016
Atu027 prevents pulmonary metastasis in experimental and spontaneous mouse metastasis models
Ansgar Santel1, Manuela Aleku, Nadine Röder
1Silence Therapeutics AG, Robert-Rössle-Strasse 10, Otto-Warburg-Haus 80, Berlin,Germany.
Purpose:
Atu027, a novel RNA interference therapeutic, has been shown to inhibit lymph node metastasis in orthotopic prostate cancer mouse models. The aim of this study is to elucidate the pharmacologic activity of Atu027 in inhibiting hematogenous metastasis to the target organ lung in four different preclinical mouse models.
Experimental Design:
Atu027 compared with vehicle or control small interfering RNA lipoplexes was tested in two experimental lung metastasis models (Lewis lung carcinoma, B16V) and spontaneous metastasis mouse models (MDA-MB-435, MDA-MB-231, mammary fat pad). Different dosing schedules (repeated low volume tail vein injections) were applied to obtain insight into effective Atu027 treatment. Primary tumor growth and lung metastasis were measured, and tissues were analyzed by immunohistochemistry and histology. In vitro studies in human umbilical vein endothelial cells were carried out to provide an insight into molecular changes on depletion of PKN3, in support of efficacy results.
Results:
Intravenous administration of Atu027 prevents pulmonary metastasis. In particular, formation of spontaneous lung metastasis was significantly inhibited in animals with large tumor grafts as well as in mice with resected primary mammary fat pad tumors. In addition, we provide evidence that an increase in VE-cadherin protein levels as a downstream result of PKN3 target gene inhibition may change endothelial function, resulting in reduced colonization and micrometastasis formation.
Conclusion:
Atu027 can be considered as a potent drug for preventing lung metastasis formation, which might be suitable for preventing hematogenous metastasis in addition to standard cancer therapy.
Insights
Atu027, an RNA interference therapeutic, effectively prevents lung metastasis in preclinical models. This novel drug inhibits cancer cell spread to the lungs, offering potential as an adjunct cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- RNA Therapeutics
Background:
- Lymph node metastasis in prostate cancer is a significant clinical challenge.
- RNA interference (RNAi) therapeutics offer targeted gene silencing mechanisms.
- Atu027 has demonstrated efficacy in inhibiting lymph node metastasis in prostate cancer models.
Purpose of the Study:
- To evaluate the pharmacologic activity of Atu027 in preventing hematogenous lung metastasis.
- To assess Atu027's efficacy across diverse preclinical mouse models of cancer metastasis.
- To elucidate the molecular mechanisms underlying Atu027's anti-metastatic effects.
Main Methods:
- Atu027 was administered via tail vein injections in experimental and spontaneous lung metastasis models.
- Models included Lewis lung carcinoma, B16V melanoma, and human breast cancer xenografts (MDA-MB-435, MDA-MB-231).
- Primary tumor growth, lung metastasis, and molecular changes (PKN3, VE-cadherin) were analyzed.
Main Results:
- Intravenous Atu027 significantly inhibited pulmonary metastasis formation in multiple models.
- Efficacy was observed in models with large primary tumors and after tumor resection.
- PKN3 inhibition by Atu027 led to increased VE-cadherin, potentially reducing endothelial cell colonization.
Conclusions:
- Atu027 demonstrates potent activity in preventing lung metastasis formation.
- Atu027 shows promise as a therapeutic agent for preventing hematogenous metastasis.
- This RNAi therapeutic may complement standard cancer treatments.
