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2024 The John Black Charitable Foundation – PCF Young Investigator Award

Validation and Clinical Qualification of Biomarkers Associated with PC Inflammation That Have Multi-Purpose Clinical Utility

Arian Lundberg, PhD
Institute of Cancer Research

Mentors: Johann de Bono, MD, PhD; Marco Bezzi, PhD; Wei Yuan, PhD

Description:

  • Biomarkers that enable early stratification of patients who have indolent vs. aggressive forms of prostate cancer will aid significantly in improving patient management, treatment, and outcomes.
  • Dr. Arian Lundberg and team have previously developed a liquid biopsy (blood draw) based gene expression biomarker that could distinguish patients with indolent vs. aggressive prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC) with a poor vs. better prognosis. This biomarker included primitive myeloid cell genes, suggesting a role for prostate inflammation in driving aggressive features of prostate cancer.
  • In this project, Dr. Lundberg and team will validate this biomarker and uncover the biology of this myeloid signature in aggressive prostate cancer.
  • The myeloid-associated whole blood RNA-signature biomarker will be analytically validated and clinically qualified using patient samples from previous clinical trials and in animal models. 
  • Whether the biomarker correlates with immune-related features such as blood neutrophil/lymphocyte ratios, myeloid-derived-suppressor-cell (MDSC) gene expression signatures, and response to treatment with a myeloid cell blocking agent, will be determined. 
  • Whether the biomarker is associated with immune cell infiltration and immune activities in mCRPC biopsies will be investigated. Whether there are any associations with clonal hematopoiesis of indeterminate potential (CHIP), an aberrant age-related condition linked to inflammation-related diseases, will also be studied.
  • If successful, this project will result in a validated multi-purpose non-invasive assay that can stratify aggressive prostate cancer and detect inflammatory processes impacting prostate cancer growth, therapy resistance, and carcinogenesis.

What this means to patients: New biomarkers for predicting the biology and outcomes of prostate cancer in patients will guide better individualized patient management and provide insights into new treatments.Dr. Lundberg has previously developed a biomarker for predicting aggressive prostate cancer, which is associated with the activity of myeloid cells, a type of immune cell that can promote prostate cancer growth. This project will validate the clinical utility of this non-invasive biomarker and uncover inflammation-associated mechanisms that drive prostate cancer progression and treatment resistance. Monitoring these inflammatory markers in blood tests could improve the care of patients facing lethal disease, and guide innovative treatment strategies