Systemic treatment of microRNA therapeutic targeting miR-10b inhibits breast cancer metastasis

Mar 30 2010

Regulus Therapeutics Inc. today announced the publication of new results in the journal Nature Biotechnology by Regulus scientists and collaborators. The new study demonstrated that systemic treatment of a microRNA therapeutic targeting microRNA-10b in tumor-bearing mice inhibits breast cancer metastasis. Cancer-related metastasis is a major cause of mortality and current cancer treatments have limited utility suppressing the metastatic spread of cancer cells. microRNA therapeutics targeting miR-10b represent a promising approach for the discovery and development of a novel anti-metastatic agent.

“Recent reports provide evidence that microRNAs are involved in cancer initiation, progression, and metastasis. Targeting miR-10b represents a promising approach for the research and development of a new anti-metastatic therapy for breast cancer.”

"We are very excited by our continued progress in developing microRNA therapeutics for the treatment of cancer. microRNAs are evolutionarily conserved regulators of gene networks and are often dysregulated in cancer. Targeting biological pathways by inhibiting microRNAs holds considerable promise as a novel therapeutic strategy for cancer and other human diseases," said Peter S. Linsley, Ph.D., Chief Scientific Officer of Regulus. "The promising data in this Nature Biotechnology publication further validates Regulus' microRNA product platform built on the integration of biology, chemistry, and bioinformatics. Working closely with our collaborators, the data generated from these efforts advance our understanding of microRNA biology in cancer. Further studies in additional animal models will help us determine the breadth of the therapeutic potential of anti-miRs targeting miR-10b."

The new paper (Ma et al. (2010) Nature Biotechnology, advanced online publication, 28 March 2010 (doi:10.1038/nbt.1618)) describes the therapeutic targeting of microRNA-10b in an in vivo mouse model of cancer metastasis. Increased levels of miR-10b have been found to be associated with high-grade malignancy; miR-10b is also found to be highly expressed in metastatic breast tumor samples from patients. Indeed, the over-expression of miR-10b in non-metastatic breast cancer cells confers invasive and metastatic characteristics. In this study, miR-10b was targeted in vivo with an anti-miR-10b oligonucleotide in a mouse tumor metastasis model. Cancer cells were implanted in the mammary fat pad of mice, forming primary breast tumors that rapidly metastasize to the lung with 100% incidence. Mice treated with PBS or a control compound rapidly developed macroscopically visible pulmonary metastases. In contrast, an 86% decrease in macroscopically visible pulmonary metastases was achieved with the anti-miR-10b treatment. This therapeutic efficacy occurred in the absence of inhibition of growth of the primary tumor, demonstrating the specific effect of anti-miR-10b on the metastatic process.

"Most cancer-related mortality is caused by metastasis, which is inadequately addressed by current cancer treatments," said Hubert C. Chen, M.D., Vice President of Translational Medicine. "Recent reports provide evidence that microRNAs are involved in cancer initiation, progression, and metastasis. Targeting miR-10b represents a promising approach for the research and development of a new anti-metastatic therapy for breast cancer."

Cancer metastasis is a complex, multi-step process by which primary tumor cells invade adjacent tissue, enter the systemic circulation, and proliferate into a secondary tumor elsewhere in the body. Metastatic disease to the lung is common and frequently involves cancerous cells arising from primary breast tumors. Previous studies have shown miR-10b to be highly expressed in metastatic breast cancer cells and involved in the regulation of cell migration and invasion (Ma et al. (2007) Nature 449, 682-689).

In the field of microRNA therapeutics, Regulus controls fundamental patent rights related to miR-10b, including compositions of matter for various anti-miR compounds targeting miR-10b, and uses of these compounds as in vivo inhibitors of miR-10b activity.