Invisible signals, visible dilemmas: The ethical frontiers of liquid biopsy in precision oncology

This critical review synthesizes the ethical, technical, and equity dilemmas emerging from the rapid clinical translation of liquid biopsy technologies in precision oncology. We analyze challenges across key domains, including diagnostic uncertainty and overdiagnosis, assay validation and tumour fraction estimation, artificial intelligence (AI)-driven interpretation, data governance, and equitable access. Building on this analysis, we propose conceptual frameworks to guide the responsible adoption of liquid biopsy in precision oncology. Major barriers to implementation include the technical and analytical limitations that generate false positives, false negatives, and "uninformative" results. A persistent gap between evidence and innovation means that many applications have strong prognostic validity but limited proven clinical utility. Emerging AI diagnostics also function as "black boxes," creating additional risks of algorithmic bias. Inconsistent data governance, high costs, and fragmented reimbursement policies further widen disparities in access, particularly for vulnerable populations, and undermine the potential of liquid biopsy to advance health equity. We conclude that a paradigm shift from reactive problem-solving to proactive, multi-stakeholder governance is essential. Using two linked frameworks, the Ethico-Clinical Cascade and the Pillars of Trust, we outline how technological innovation should be aligned with robust ethical oversight, transparent communication, and equity-focused policies so that liquid biopsy reduces, rather than reinforces, the global cancer burden.