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2024 The John & Daria Barry Foundation – PCF Young Investigator Award

A Novel Liquid Biopsy Assay Using Circulating Tumor Extracellular Vesicles to Monitor Prostate Cancer Tumor Evolution and Emergence of Drug Resistance

Irene Casanova-Salas, PhD
Vall d’Hebron Institute of Oncology 

Mentor: Joaquin Mateo, MD, PhD

Description:

  • Understanding the mechanisms of therapy resistance and heterogeneity within metastatic prostate cancer is crucial for developing effective treatment strategies. Traditional metastatic biopsy methods are invasive and do not capture dynamic changes in biology over time or across all sites of disease. Liquid biopsies (blood draws) offer a promising alternative for non-invasive monitoring of tumor dynamics, yet their utility for measuring tumor gene expression has been limited by the rapid degradation of RNA in circulation. 
  • Dr. Irene Casanova-Salas has developed methods for using tumor-derived extracellular vesicles (EVs) to interrogate tumor genomics and gene expression in liquid biopsies. She has previously shown that EVs recapitulate tumor mutations and associate with clinical progression, and are a feasible method for evaluating tumor gene expression over time. 
  • This project will evaluate the utility of integrative genomic and gene expression profiling of EVs from liquid biopsies using larger clinical cohorts and preclinical models.
  • The clinical relevance of EV-DNA and circulating tumor DNA (ctDNA) kinetics in patients and preclinical models treated with different therapies will be assessed. Molecular imaging (MRI/PET) will also be integrated to study tumor evolution and intra-patient heterogeneity.
  • EV-RNA based biomarkers will be developed to aid patient stratification and development of personalized therapeutic approaches. 
  • If successful, this project will result in novel liquid-biopsy based biomarkers that provide insights into how prostate cancer evolves under therapy and can aid in individualized treatment selection for patients.   

What this means to patients: New technologies using liquid biopsies offer the potential for studying tumor biology and evaluating how tumors change over time, particularly during treatment. Dr. Casanova-Salas is developing novel liquid biopsy biomarkers that will advance our understanding of metastatic prostate cancer biology and drug resistance mechanisms, and enable personalized therapeutic