Opportunities for Liquid Biopsies to Meet the Challenges of Precision Medicine

Liquid biopsies provide many opportunities for developing biomarkers to detect and monitor cancers and are critically important to the practice of precision medicine. These biomarkers may be alternatives or complementary to tissue biopsy and anatomical and functional imaging, and such biomarkers are relevant for drug development and patient care. Since they are minimally invasive and potentially more sensitive than tissue-based biomarkers, they may help detect early stages of disease onset and progression, as well as for serial monitoring of patient treatment. Biomarkers developed in liquid biopsies may be predictive (e.g., companion or complementary diagnostics), may be indicative of response to treatment and emerging resistance, provide information for treatment selection, and may prove helpful for early detection of disease. Increasing understanding of cancer biology and widespread availability of advanced technologies involving single-cell analysis, high-definition imaging, nanotechnology, and genomic, proteomic, and immune system analysis allow the unprecedented proliferation of liquid biopsy assays. This expansion has led to challenges for ensuring the reliability of these assays from both scientific and regulatory perspectives. Research on ctDNA provides examples of how these challenges are being met, such as through standardized protocols, regulatory guidance on levels of evidence required for assays, advancing drug development based on these assays, and the use of control materials to support the reliability of assays and comparability of results obtained across assays. Collaborative efforts among all stakeholders are critical to meeting these challenges.