Liquid biopsy analysis to refine prognosis in renal cell carcinoma
Lay Abstract
Incidence rates for kidney cancer are rising worldwide. Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer account for about 80% of all cases. Most patients undergo surgical removal of the kidney or tumor but a third of these patients develop relapse or metastasis, which is life-threatening. However, it remains difficult to predict risk of relapse or metastasis post-surgery among ccRCC patients. Thus, there is an urgent need to identify factors that can reliably predict risk of relapse/metastasis to establish personalized and effective management strategies for ccRCC. We and others have shown that gene mutations in ccRCC tumors may be used to estimate the risk of relapse in patients Further, our team has shown that cell-free tumor DNA (ctDNA) released by tumor cells can be identified in biofluids (blood or urine) offering unique opportunities for non-invasive genetic tests through liquid biopsy screening in ccRCC.
Objectives and research plan: The objectives of this study are therefore to develop a robust and non-invasive assay that will allow for sensitive and specific detection of tumor mutations in the blood or of ccRCC patients (liquid biopsy), particularly in patients at high-risk for relapse. We will assess the feasibility and utility of liquid biopsy analysis using cutting-edge technologies including next-generation sequencing (NGS), for the detection of tumor mutations as a tool for ccRCC patient stratification, and disease monitoring. Our study will benefit from in-house state-of-the-art genomics and bioinformatics infrastructure, access to well-characterized patient cohorts, and expertise in genomics, tumor biology, tumor extracellular vesicles, and clinical management of ccRCC.
Significance: There is a growing population of patients, suffering from metastatic ccRCC and long-term side effects of treatment. The emotional/economic burdens of RCC on patients, families and society are significant. Identifying and implementing prognostic genetic markers in clinical practice will help clinicians improve health-care delivery to patients based on individualized risk assessment.
Outcomes of this study have the potential to significantly impact patient management, allowing accurate risk stratification for recurrence/progression, timely identification of patients with failure, better adapted follow up regimens, and potentially better selection of candidates for adjuvant treatments. Ultimately, this study will provide tangible benefits for patients affected by ccRCC and greatly impact ccRCC patient care and management worldwide.
