Global Circulating Free DNA Methylation in Metastatic Renal Cell Carcinoma Patients (GOLDEN)
Project Title: Global Circulating Free DNA Methylation in Metastatic Renal Cell Carcinoma Patients (GOLDEN)
Project Duration: 2021-2023
MOHCCN Consortium: Princess Margaret Cancer Consortium
Investigators: Dr. Aaron Hansen, Dr. Lillian Siu, Dr. Pavlina Spiliopoulou, Dr. Brooke Wilson, Dr. Nazanin Fallah-Rad, Dr. Adrian Sacher, Dr. Srikala Sridhar
- Princess Margaret Cancer Centre
- To evaluate changes in cfDNA methylation profiles in patients with mRCC following exposure to immunotherapy.
- To correlate cfDNA methylation profiles, at baseline and during treatment, with disease response to immunotherapy.
Immunotherapy is a standard of care treatment for patients with metastatic renal cell carcinoma (RCC), but unlike other cancer types, there are no predictive biomarkers of response to it. New biomarkers are critically needed to help identify those most likely to benefit and to enable us to characterize disease response to treatment with greater detail. Circulating free DNA (cfDNA) has emerged as a practical, non-invasive biomarker of disease monitoring, however mRCC is associated with low yields of cfDNA in the peripheral blood. The GOLDEN study suggests an alternative approach in describing disease activity with the detection of cell-free methylated DNA by immunoprecipitation-based sequencing (cfMeDIP-seq). cfMeDIP has been found to be more sensitive than conventional ctDNA detection approaches in mRCC and can be performed even when access to tumor sample is impossible. With GOLDEN, there is an opportunity to use a novel, non-invasive and tumor-independent biomarker to monitor disease dynamics and predict disease response in mRCC.