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2020 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

Daniel Khalaf, MD

BC Cancer Agency

Mentors: Kim Chi, MD; Alexander Wyatt, PhD

Description:

  • Precision medicine is an emerging treatment strategy for patients with prostate cancer, in which treatments for individual patients are selected based on their unique tumor biology, such as tumor mutations. Determination of tumor mutations has required invasive tumor biopsies, which are often difficult or not possible in patients with metastatic disease.
  • Dr. Daniel Khalaf is studying tumor DNA released into the circulation as a non-invasive biomarker (aka, liquid biopsy) in prostate cancer patients to inform outcomes and optimize treatment selection.
  • In previous studies, circulating tumor DNA fraction (%) showed the highest correlation with treatment outcomes, and undetectable levels identified a subgroup of patients with a very favorable prognosis.
  • Dr. Khalaf will prospectively validate whether an undetectable level of circulating tumor DNA is a strong and independent biomarker of favorable outcomes in patients with metastatic castration resistant prostate cancer(mCRPC) undergoing standard of care treatments.
  • In patients who have detectable levels of circulating tumor DNA, tumor mutations will be determined and used in combination with circulating tumor DNA fraction and clinical disease characteristics to develop a refined biomarker for optimal treatment selection.
  • Dr. Khalaf will also investigate primary tumor mutations in patients with localized prostate cancer who have undetectable levels of circulating tumor DNA, in order to understand the biology of this favorable prognostic subgroup and potentially identify patients at risk of poor outcomes.
  • If successful, this project will result in the development of non-invasive biomarkers to predict outcomes and inform treatment selection for prostate cancer patients.

What this means to patients: Dr. Khalaf is developing non-invasive, blood-based biomarker tests that evaluate circulating tumor DNA levels and tumor mutations 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.