Princeton Docket # 12-2807
Researchers in the Molecular Biology Department at Princeton University have discovered a group of miRNAs as novel therapeutics for bone metastasis. Through a series of in vitro and in vivo experiments, five distinctive miRNAs have been identified as inhibitors of osteoclast differentiation. Further, systemic treatment with the miRNAs in mice xenografted with highly metastatic breast cancer cells resulted in a remarkable reduction in tumor burden and bone lesion area, uncovering the potential for novel miRNA-based therapeutics in bone metastasis.
Parallel studies examining two other miRNAs, both of which increased in expression during osteoclast differentiation, revealed the potential for miRNA-based biomarkers for bone metastasis progression. Specifically, levels of these miRNAs are discovered to be well correlated with metastatic disease stages and bone metastasis burden, as demonstrated in mouse serum samples. Preliminary studies in human tissues also revealed higher expression of these miRNAs in bone metastasis tissues than matched primary tumors.
Bone metastasis is present in the vast majority of late-stage patients of breast, prostate and many other types of cancer, leading to pain, pathological fractures, nerve compression, hypercalcemia and many other severe complications. Osteoclasts are a key component in bone metastasis, congregating at the site of the developing metastatic lesion and resorbing the bone, which in turn releases sequestered growth factors that further enhances tumor expansion. Current treatments targeting osteoclasts, such as bisphosphonoates and denosumabs are able to limit the pathology associated with bone metastasis, although without significant improvement to the survival of patients. Therefore, there is a strong demand for novel therapeutics and early diagnostic markers.
Applications
· Therapeutics for bone metastasis
· Biomarker for
Ø Early detection of bone metastasis
Ø Monitoring of therapeutic response
Ø Indication of disease stage
Ø Prognosis
Advantages
· Novel mechanism of action
· Sensitive and non-invasive serum marker
Inventor
Yibin Kang is Professor of Molecular Biology and a leading expert in cancer metastasis. The central theme of his research is a multidisciplinary and integrative approach to the analysis of the molecular basis of cancer metastasis, combining molecular biology and genomics tools with animal models and advanced in vivo imaging technologies. His work is focused on the identification of metastasis genes and functional characterization of their involvement in tumor-stromal interactions during the formation of metastasis in different organs and is also interested in regulators of mammary gland development and early oncogenic events that may have significant impact on tumor progression and metastasis. Dr. Kang's outstanding achievements have been recognized by many prestigious awards, including AACR Award for Outstanding Achievement in Cancer Research (2012), Vicek Prize for Creative Promise in Biomedical Sciences (2011), and Department of Defense Era of Hope Scholar Award (2006).
Brian Ell is a graduate student in Prof. Kang¿s lab.
Intellectual Property & Development status
Patents protection is pending and experimental data are available under appropriate confidentiality agreements.