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2023 Royalty Pharma – PCF Young Investigator Award

Investigating Tumor and Immune Cell Dysregulation for the Treatment of Prostate Cancer Bone Metastases

Shenglin Mei, PhD
Harvard: Massachusetts General Hospital (MGH)

Mentors: David Sykes, Philip Saylor

Description:

  • The bone and bone marrow are metastatic sites in ~90% of patients with metastatic castration-resistant prostate cancer (mCRPC), and show poor responses to second-generation anti-androgen treatments and immunotherapies. There is an urgent need to better understand the processes underlying prostate cancer bone metastases, and to use this information to develop better treatments for our patients.
  • An important feature that accompanies the progression of prostate cancer is the remodeling of the tumor and immune cell microenvironment, ultimately leading to dysregulated and tumor-supporting immune cell populations.
  • Dr. Shenglin Mei is using single cell and spatial gene expression data from primary prostate cancer and bone metastatic tumor samples to investigate the role of tumor and immune cell remodeling and their specific cell to cell interactions in bone metastasis.
  • The characteristics of functionally distinct tumor subclusters in the progression from localized to metastatic disease will be determined.
  • Immune cell dysregulation and key cell-to-cell nodes of communication with each tumor cell cluster will be investigated.
  • The clinical implications of tumor sub- clustering and immune cell interactions in prostate cancer and other malignancies will be determined.
  • If successful, this project will provide deeper understandings of tumor cell and immune cell heterogeneity, dysregulation, and interactions that contribute to prostate cancer bone metastasis and disease progression. These mechanistic insights will aid in the development of new therapeutic strategies for patients with prostate cancer bone metastases.

What this means to patients: Prostate cancer commonly metastasizes to the bone, and these lesions are often highly resistant to standard and experimental therapies. Dr. Mei and team are comprehensively characterizing the tumor and immune cell types, locations, functions, and cell-cell interactions in bone metastases. These studies will provide new insights into prostate cancer biology and enable the development of new, improved treatment strategies.