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2021 John Black Charitable Foundation-PCF Young Investigator Award

Genomic Tracking of Advanced Prostate Cancer Leveraging Bespoke Assays

Emily Grist, MBBS
University College London Cancer Institute

Description:

  • A number of trials have demonstrated the clinical benefit of adding chemotherapy or androgen receptor (AR)-targeted therapies to androgen deprivation therapy (ADT) in advanced hormone sensitive prostate cancer (HSPC). Additional treatments such as PARP inhibitors continue to be tested in this clinical space. With these multiple treatment options, emerges the need for biomarkers to guide treatment selection for individual patients.
  • Dr. Emily Grist is developing circulating tumor DNA-based biomarkers to aid in treatment selection and for early detection of treatment resistance.
  • In this project, Dr. Grist will develop a pipeline for using whole genome sequencing to detect circulating prostate cancer DNA from patient plasma samples, and study tumor genomic alterations and tumor burden.
  • The ability of this assay to detect minimal residual disease and emerging resistant tumor clones will be tested using samples from two large clinical trials, PARADIGM and STAMPEDE.
  • This test will then be used to prospectively detect and characterize circulating tumor DNA from the first precision therapy arm in the STAMPEDE trial, testing PARP-inhibitors in patients with a DNA damage repair (DDR) gene defect.
  • If successful, this project will result in a non-invasive test that uses patient blood samples to evaluate tumor DNA, select treatments, and monitor treatment response and resistance.

What this means to patients: Circulating tumor DNA can be obtained from patient blood samples and used to study tumor biology. Dr. Grist is developing a circulating tumor DNA test that will act as a biomarker for informing personalized treatment selection, monitoring treatment response and resistance, identifying patients that may benefit from a treatment switch or intensification, and studying tumor genomics and treatment resistance mechanisms.