Positive research findings suggest Silence Therapeutics’ lead RNA interference (RNAi) drug candidate, Atu027, could prevent the formation of pulmonary metastasis in various animal models of cancer metastasis.
Researchers showed that Atu027 inhibited multiple key biological processes that enable and contribute to the dissemination and formation of pulmonary metastases in a murine breast cancer metastasis model. Breast cancer cells prefer to metastasize through the bloodstream to the lung.
The findings were published in the latest edition of the scientific journal Clinical Cancer Research in a peer-reviewed paper entitled Atu027 Prevents Pulmonary Metastasis in Experimental and Spontaneous Mouse Metastasis Models.
Atu027 is a proven inhibitor of the expression of PKN3, a molecule that is believed to play an important role in the progression of cancer and metastasis formation in particular.
In the study, researchers administered Atu027 to multiple mouse models of breast cancer to evaluate the drug’s ability to prevent the spread of the cancer to the lungs.
Study data demonstrated that Atu027 has a clear inhibitory effect on the formation of pulmonary metastasis.
With metastasis directly linked to high rates of mortality in cancer patients, the prevention of metastasis dissemination and formation is a critical goal of cancer treatment.
Klaus Giese, PhD, chief scientific officer at Silence Therapeutics, said: “While the demonstrated inhibition of pulmonary metastasis formation was a positive and important outcome of this study, equally important is what we learned regarding the manner in which Atu027 is able to achieve this effect.”
He said: “These findings showed that in addition to our previously published research demonstrating its ability to inhibit metastasis through the lymphatic system, Atu027 also appears to interrupt the metastatic processes that involve blood flow to the lung.
”Importantly, these data provide us with evidence that Atu027, which targets vascular endothelial cells, may be modulating not only the tumor vasculature itself, but the pulmonary vasculature as well.”
Philip Haworth, PhD, chief executive officer of Silence Therapeutics, said: “We are very pleased to be able to continue to identify the mechanisms that drive Atu027’s therapeutic activity while concurrently advancing the product through its ongoing Phase 1 study.
”Building this collection of novel data on Atu027 will only serve to inform our ongoing development efforts and allow us to maximize the opportunity for success with this program.”
Atu027, a liposomal AtuRNAi(TM) formulation in clinical development for systemic cancer indications, is one of the most clinically advanced RNAi therapeutics in the area of oncology.
In June 2009, Silence initiated an open-label, single-centre, dose-escalation Phase I study with Atu027 in patients with advanced solid (malignant) tumors involving single, as well as, repeated intravenous administration.
The study is expected to be completed early in the second half of 2011.