Tumor Microenvironment and Metastasis
OUR MISSION
T he long-term goal of our team is understanding and treating cancer bone metastases, drug resistance, and recurrence. Mechanisms of bone metastases are largely unknown, which impedes the development of new treatments. Our unique strategy is to target not only malignant cells, but also non-malignant cells in the tumor microenvironment. We use genetically-engineered and experimental mouse models, bioinformatics analyses, virtual drug screening, and artificial intelligence drug design to answer the scientific questions and achieve our long-term goals.
In the past years, our group has discovered 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 in 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. Recently, we discovered that enzalutamide induces PTH1R-mediated TGFBR2 degradation in osteoblasts may confer the drug resistance in prostate cancer bone metastases.
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.
11.17.2023 We got three DOD grants!
11.09-12.2023 Dr. Li made a presentation in the SBUR 2023 Annual Meeting and Yawei was honored with TRAVEL AWARD.
10.13.2023 Yawei got the ASBMR travel award and his poster was selected for presentation at ASBMR annual meeting.
OUR RESEARCH
Influence of bone microenvironment on prostate cancer bone metastases and drug resistance (Project leader – Dr. Shang Su)
O ver 80% prostate cancer deaths are involved with bone metastases. 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. This study is currently supported by an R01 (2019-2024) from NCI.
Influence of bone microenvironment on tumor dormancy and reactivation (Project leaders – Dr. Shang Su & Ms. Ruihua Liu)
I t has been proposed that the early disseminated tumor cells are the cells of origin for cancer recurrence. Up to 70% of prostate cancer patients have disseminated tumor cells in the bone marrow at the time of initial diagnosis. These cells remain dormant initially but proliferate later to overt metastases that eventually kill patients. Understanding the mechanisms of dormancy and reactivation will provide novel avenues for metastases prevention and inhibition.
Drivers of bone-specific metastasis (Project leaders – Drs. Shang Su & Yawei Zhao)
D rivers for bone-specific metastasis and subsequent bone destruction are still largely unknown. Applying bed to bench side approach. We collaborate with Bin Chen’s (MSU) team analyzing big data of patient and virtual drug screening to instruct our basic research in determining the drivers and testing the efficacy of targeting at pre-clinical setting.
Intermittent fasting effects on bone metastasis and drug resistance (Project leader – Dr. Yawei Zhao)
I n recent years, intermittent fasting has been shown many health benefits that are not simply the result of weight loss. Many clinical trials of intermittent fasting in cancer patients are currently in progress. However, no conclusive benefits in cancer incidence, metastasis, treatment responses or drug resistance are reached. Using our unique preclinical mouse models, we aim to answer these questions and further determine the mechanisms of the actions at molecular and cellular level.