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2021 Peter and Laurie Grauer in Honor of Plum and Jonathan W. Simons, MD-PCF Young Investigator Award

Development of High-Performance Liquid Biopsy in Prostate Cancer through Enhanced Cell-Free DNA Recovery

Shervin Tabrizi, MD
Harvard: Massachusetts General Hospital

Mentors: John Christopher Love, PhD, Viktor Adalsteinsson, PhD, Anthony V D’Amico, MD, PhD

Description:

  • Precision medicine in management of prostate cancer requires biomarkers that can enable individualization of treatment, sensitive and early detection of disease recurrence, and monitoring of disease response on therapy.
  • Circulating tumor DNA (ctDNA) has enormous promise for this purpose, as it can be obtained non-invasively via a simple blood draw and be used to study tumor genomics and tumor burden. However, current ctDNA assays are limited by poor sensitivity due to the limited quantity of tumor DNA shed into the bloodstream in common clinical settings.
  • Dr. Shervin Tabrizi is developing a novel technology to increase the amount of ctDNA sampled in a blood draw to improve ctDNA liquid biopsy tests.
  • In this project, Dr. Tabrizi will engineer and synthesize novel DNA-protectors that can inhibit degradation and clearance of cell-free DNA, thereby increasing the quantity and quality of ctDNA that can be obtained from blood draws.
  • The most promising DNA-protectors identified will be tested in animal prostate cancer models to determine safety, toxicity and efficacy.
  • If successful, this project will result in development of an intravenous molecular agent that improve the recovery of ctDNA, and thereby expand the ability to use ctDNA tests in clinical settings.

What this means to patients: Circulating tumor DNA (ctDNA) testing using blood samples from patients has the potential to enable monitoring of disease progression, treatment resistance, and selection of precision medicines. However, these tests require improvement before they can be widely used in clinical practice. Dr. Tabrizi will develop a new molecular agent that can be administered to patients that improves the sensitivity and accuracy of ctDNA testing, enabling it to be used in a broad array of prostate cancer clinical settings to inform management decisions and improve outcomes.