Landmark Perspective Charts the Path from Approved Liquid Biopsy Assays to ctDNA-Guided Relapse Detection
This Nature Reviews Clinical Oncology perspective surveys the current state of liquid biopsy implementation, from FDA-approved single-gene and multigene companion diagnostics to emerging applications in early-stage disease monitoring. The authors introduce the concept of 'ctDNA relapse' -- molecular detection of residual disease before imaging-detected recurrence -- as the next clinical frontier. Key gaps in technology, trial design and clinical workflow integration are identified as barriers to broader adoption.
The original study
Liquid biopsy enters the clinic - implementation issues and future challenges.
- Authors
- Ignatiadis M, Sledge GW, Jeffrey SS
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 33473219
Original abstract
Historically, studies of disseminated tumour cells in bone marrow and circulating tumour cells in peripheral blood have provided crucial insights into cancer biology and the metastatic process. More recently, advances in the detection and characterization of circulating tumour DNA (ctDNA) have finally enabled the introduction of liquid biopsy assays into clinical practice. The FDA has already approved several single-gene assays and, more recently, multigene assays to detect genetic alterations in plasma cell-free DNA (cfDNA) for use as companion diagnostics matched to specific molecularly targeted therapies for cancer. These approvals mark a tipping point for the widespread use of liquid biopsy in the clinic, and mostly in patients with advanced-stage cancer. The next frontier for the clinical application of liquid biopsy is likely to be the systemic treatment of patients with 'ctDNA relapse', a term we introduce for ctDNA detection prior to imaging-detected relapse after curative-intent therapy for early stage disease. Cancer screening and diagnosis are other potential future applications. In this Perspective, we discuss key issues and gaps in technology, clinical trial methodologies and logistics for the eventual integration of liquid biopsy into the clinical workflow.