Yusuke Shiozawa Laboratory

Patients with bone metastases and their families pay a tremendous price physically and emotionally. As a physician dealing with patients suffering from bone metastases, I realized that there was a need to learn more about how primary tumors progress to co-opt bone marrow. Our laboratory plans to continue this quest, exploring the following areas in the next few years: 

1) Determine how the bone marrow microenvironment affects the bone metastatic process.

The bone marrow microenvironment influences how disseminated tumor cells are regulated, but how it does so in active bone metastasis remains unclear. 

Toward this goal

       I.      We will identify metabolic molecular mechanisms by which the bone marrow microenvironment may control tumor dormancy and recurrence through fatty acid metabolism.

     II.        We will identify molecular mechanisms behind the mysterious but crucial roles bone marrow mast cells play in bone metastasis.  Mast cells have been known to participate in the tumor microenvironment, but full understanding of their function in active bone metastasis remains elusive.

I am confident that targeting metastatic tumor cells alone is of limited therapeutic value; targeting the microenvironment as well is critical for eliminating bone metastasis.

2) Determine how the crosstalk between metastatic cells and marrow nerve cells controls bone cancer pain.

Cancer-related pain, both its causes and its management, poses a tremendous challenge to patients and their caregivers. Indeed, a full 80% of patients with bone metastasis suffer from cancer-induced bone pain, however little is know about the possible molecular mechanisms involved. In this study, our group will focus on fundamental mechanisms behind the provocative concept that crosstalk between metastatic cells and bone marrow nerves controls cancer-induced bone pain. I believe that the insights derived from our investigations will lead to new strategies to improve the quality of life of cancer patients.

3) Identify novel and effective treatments for bone metastasis, using hematopoietic stem cells to deliver nanoparticles to the bone marrow.

To pursue this goal, we will develop a unique drug delivery system to target bone metastasis using the homing ability of hematopoietic stem cells. By developing a more effective and safer therapeutic delivery system directly to bone marrow, this study will lay the foundation for significant improvements in the care of cancer patients, allowing local use of more potent anti-cancer drugs that might not be well-tolerated systemically at high concentrations.

My long-term commitment to and experience in establishing a direct link between the bone marrow microenvironment and metastatic disease puts these goals in reach, which can lead to breakthroughs in extended cancer treatments and improved quality of life for patients.

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Cancer Biology

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