Potential adoption of electrochemical biosensors for cancer DNA biomarker detection in liquid biopsies: A systematic review.

[BACKGROUND] The detection of actionable DNA biomarkers in liquid biopsies is essential for advancing precision oncology. While conventional techniques such as PCR and NGS are highly accurate, their high cost, complexity, and slow turnaround time limit widespread clinical applications. Electrochemical biosensors present a promising alternative through their portability, affordability, and rapid analysis capabilities.

[OBJECTIVE] This systematic review evaluates the current status and potential clinical adoption of electrochemical biosensors for detecting cancer DNA biomarkers in liquid biopsies, focusing on their sensitivity and specificity compared to standard PCR-based methods.

[METHODS] A comprehensive search across PubMed, Scopus, and Web of Science was conducted up to August 2025, yielding 1723 articles. After applying PRISMA guidelines with strict inclusion and exclusion criteria, 31 studies were selected. The quality of the selected studies was assessed using the SURE checklist. Data on biosensor design, amplification strategies, detection limits, and clinical applicability were extracted.

[RESULTS] Most biosensors achieved femtomolar to attomolar detection limits (LODs), reaching the required sensitivity limits for germline and somatic mutations respectively These LODs were achieved primarily via signal amplification strategies using redox mediators, nanomaterials, and strand displacement assays. Target amplification was less common and did not demonstrate consistent superiority. Specificity was enhanced through modified probes, enzymatic cleavage, magnetic separation, and blocking agents, though assessment methods varied. In general, covalently immobilized probes improved stability and sensitivity. However, most assays were validated in buffer with synthetic DNA, limiting clinical relevance.

[CONCLUSIONS] With respect to their performance, electrochemical biosensors exhibit considerable potential for clinical integration. In particular when integrating different signal amplification strategies, such as a synergistic approach of redox mediators and nanocomposites, or combining target and signal amplification to reach the required sensitivity limits. Nonetheless, their clinical integration requires evaluation in complex biological samples, more thorough selectivity studies, and rigorous validation on patient samples. When standard validation assays can be provided and performed, electrochemical biosensing assays hold great promise for the detection of cancer DNA biomarkers in liquid biopsies.