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.