The Bone Microenvironment and Cancer


LI lab endeavors to treat and prevent cancer bone metastases, drug resistance, and recurrence through a better and deeper understanding of the bone microenvironment. The impacts of the bone microenvironment on these events are largely unknown. However, we know the significant roles of the tumor microenvironment in cancer initiation, progression, and drug resistance. Therefore, our unique strategy is to target malignant and non-malignant cells in the tumor microenvironment. We use genetically engineered and experimental mouse models, bioinformatics analyses, virtual drug screening, and novel drug design to answer the scientific questions and achieve our long-term goals.

In recent years, our group has discovered that TGF-β signaling in mesenchymal lineage cells inhibits, but in myeloid lineage cells promotes, bone metastasis in breast, prostate, and non-small cell lung cancers. These studies lay the foundation for the bone cell-specific role of TGF-β signaling in cancer metastases and identify potential novel drug targets for the bone microenvironment in treating bone metastases. We discovered that enzalutamide induces TGFBR2 degradation in osteoblasts, which confers drug resistance in prostate cancer bone metastases. The TGFBR2 degradation was found to be mediated by PTH1R, specifically in osteoblasts. In collaboration with experts in the field, we are currently developing novel drugs to target PTH1R. Furthermore, we discovered how treatment, such as primary tumor removal, affects prostate cancer cell dissemination and dormancy and how the dormancy of prostate cancer cells is induced.

Undergraduate, PhD, or MD/PhD students, who are interested in cancer research are welcome! Together, we are dedicated to contributing biomedical basic knowledge and improving patient care.

05.13.2024 Shang signed the offer from Louisiana State University as an Assistant Professor.

05.13.2024 Prisca joined our lab.

04.15.2024 Yawei's JCI article was accepted.


Impact of bone microenvironment on prostate cancer bone metastases and drug resistance.

Over 80% of prostate cancer deaths are involved with bone metastases. However, only 10% of the patients in the U.S. present any detectable bone metastasis at the time of diagnosis, suggesting bone metastases develop even after various curative-intended treatments. What drives the bone metastasis is unknown. Furthermore, second-line hormonal therapies such as enzalutamide improve overall patient survival only by several months in about 50% of the patients, and almost all patients develop drug resistance. There is an urgent need to determine the mechanisms of drug resistance and to develop new approaches for overcoming such resistance and for better treatment of prostate cancer bone metastasis.

Impact of bone microenvironment and treatment on tumor cell dissemination and dormancy

I t has been speculated that the early disseminated tumor cells (DTCs) are the cells of origin for cancer recurrence. These cells remain dormant initially but proliferate later to overt metastases that eventually kill patients. When and in which organs do the tumor cells disseminate? How are the DTCs induced into and maintained in dormancy? How do the dormant DTCs reactivate to proliferation? Answering these questions will provide novel avenues to prevent and treat metastases and recurrence.

Novel drug development and testing

B asic biology research reveals novel targets. Drugs might need to be developed for inhibition. PTH1R is one of the targets identified in our studies. In collaboration with experts in the field, we are currently developing and testing blocking PTH1R, including small-molecule inhibitors, DNA aptamers, and PROTAC.