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2023 Clay Hamlin, Metropoulous Family Foundation, William and Cary Singleton -PCF Young Investigator Award

Investigating how Prostate Cancer causes Sclerotic Metastatic Bone Lesions and Impact Fracture Risk using Cellular and Materials Sciences Approaches

Felipe Eltit Guersetti, DDS, PhD
University of British Columbia (UBC)

Mentors: Michael Cox, Colm Morrissey, Raphaele Charest-Morin

Description:

  • About 20% of patients diagnosed with prostate cancer will eventually develop incurable metastatic prostate cancer, with bone being the most common metastatic site.
  • Prostate cancer bone metastases cause abnormal hardening or thickening of bone that increases a patient’s risk for fractures and spinal cord compression, which can cause severe pain or even paralysis These risks are exacerbated by standard-of-care androgen deprivation therapy (ADT). The mechanisms that drive development of abnormal bone density and increase fracture risk in metastatic lesions remain unclear.
  • Felipe Eltit Guersetti is investigating the bone structure of prostate cancer bone metastases, to identify the cause of bone metastasis development and identify at-risk patients based on tumor phenotype and bone architecture.
  • In this project, Dr. Eltit and team will characterize bone architecture, mineral composition, and fracture sensitivity in bone metastatic samples from patients treated for pathologic fracture or spinal cord compression.
  • Single cell and spatial analyses will be performed on bone metastases samples to identify tumor cell profiles and bone microenvironment features that relate to fracture-prone pathologic bone architecture.
  • Preclinical bone-tumor models will be studied to evaluate how various subtypes of prostate cancer cells interact with and impact bone cell activities.
  • If successful, this project will improve understandings of how prostate cancer metastases impact bone architecture and biology and increase fracture risk. This is crucial to developing new intervention strategies to block formation of abnormal bone lesions and improve quality of life for patients with metastatic prostate cancer.

What this means to patients: Nearly all patients with metastatic prostate cancer develop bone metastases, which increase risk for fractures and spinal cord compression, causing pain and reduced quality of life. Dr. Eltit and team will characterize bone microenvironment and prostate cancer features that enable bone metastases and cause fracture-prone pathologic bone architecture. These studies will help to identify patients at risk for bone fractures and enable development of new therapeutic interventions that decrease morbidity from bone metastases.