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2022 Foundation Medicine – PCF Young Investigator Award

Developing a Novel ctDNA-Based Approach to Patient Risk Stratification and Treatment Selection in mCRPC: A Large Population-Based Cohort Study

Nicolette Fonseca, PhD

Mentors: Alexander Wyatt, D. Phil and Kim Chi, MD

Description:

  • Prostate cancer that has spread to other organs is incurable but new treatments have improved life expectancy. However, this disease is heterogeneous and can manifest with aggressive spread in some patients but remain slow growing in others. Refining treatment selection relies on tumor biomarkers that relay information about an individual’s unique tumor biology.
  • Sampling tumor material requires invasive biopsies which are difficult to perform on patients with metastatic disease. Dr. Nicolette Fonseca is studying tumor DNA (ctDNA) released into the circulation as a non-invasive biomarker (i.e., liquid biopsy) in prostate cancer patients to inform outcomes and optimize treatment selection.
  • Previous studies show that ctDNA in blood is closely linked to disease aggression, and that the quantity of ctDNA can be used to identify favorable and unfavorable prognostic subgroups.
  • Dr. Fonseca will prospectively validate in >1000 samples whether ctDNA is a strong and independent biomarker of aggressive disease in patients with metastatic castration resistant prostate cancer (mCRPC) across different treatment contexts.
  • Dr. Fonseca will build a user-friendly computational model that incorporates ctDNA together with clinical and radiographic risk factors to predict individualized life expectancy. This public and free model will be adaptable to different treatment scenarios and be able to use results from different blood ctDNA tests.
  • If successful, this project will result in the development of practical online tools that can improve physician decision making about treatment selection and intensification, patient monitoring and clinical trial enrolment.

What this means to patients: Dr. Fonseca is developing low-cost, non-invasive, blood-based biomarker tests that evaluate circulating tumor DNA levels to predict outcomes and identify optimal treatment strategies for patients. This project will greatly accelerate precision medicine and improve outcomes for patients with prostate cancer.