Challenges and proposed solutions to the adoption of cell free DNA in screening, detecting and prognosticating colorectal cancer.

Detection and treatment of colorectal cancer (CRC) at an early stage is vital for long-term survival. Liquid biopsy has emerged as a promising new avenue for non-invasive screening of CRC as well as prognostication and surveillance of minimal residual disease. Cell free DNA (cfDNA) is a promising liquid biopsy analyte and has been approved for use in clinical practice. Here, we explore the current challenges of utilizing cfDNA in the screening and prognostication of CRC but also for detecting driver mutations in healthy, presymptomatic patients with normal colonic crypts. CfDNA for the detection of cancerous or premalignant colonic lesions has already been extensively explored, however few have considered utilizing cfDNA in the detection of driver mutations in healthy patients. Theoretically, this would allow us to detect patients who are at a higher risk of tumorigenesis decades in advance of established malignancy and stratify them into higher risk groups for early-intervention screening programs. We also explore the solutions necessary to overcome the challenges that prevent liquid biopsy from entering mainstream clinical use. The potential for liquid biopsy is immense if these challenges are successfully circumvented, and can dramatically reduce CRC rates as well as improve survival in patients.