Circulating Biomarkers for Therapeutic Monitoring of Anti-cancer Agents

Abstract

Circulating biomarkers have emerged as valuable surrogates for evaluating disease states in solid malignancies. Their relative ease of access and rapid turnover has bolstered clinical applications in monitoring treatment efficacy and cancer progression. In this review, the roles of various circulating biomarkers in monitoring treatment response are described. Non-specific markers of disease burden, tumor markers (eg CA 125, CEA, PSA, etc.), circulating tumor cells, nucleic acids, exosomes, and metabolomic arrays are highlighted. Specifically, the discovery of each of these markers is reviewed, with examples illustrating their use in influencing treatment decisions, and barriers to their application noted where these exist. Finally, opportunities for future work using these circulating biomarkers are discussed.

Keywords: biomarker; ctDNA; exosomes; metabolomics; treatment response; tumor marker.

Figure 1.

Features of ideal circulating biomarker. In evaluating a circulating biomarker, various factors must be considered. The biomarker must be easily detected, quantifiable, and objectively measured. Detection of the biomarker should be inexpensive. Assays for measurement should have robust validation, with optimized sensitivity and specificity. Further, testing should be reliable/reproducible allowing for results to be standardized across different testing centers. In terms of clinical characteristics, an ideal circulating biomarker is conveniently collected through a procedure which subjects patients to minimal toxicities or adverse effects. The biomarker may be non-invasively detected. There should be opportunities for repeated assessment through a treatment course. For biologic characteristics, biologic plausibility is preferred and may facilitate interpretation and communication around testing results with patients. Rapid turnover is essential for securing real-time responses to ongoing interventions. Finally, the circulating biomarker must be validated in clinical practice and should have proven clinical utility.

Figure 2.

Strengths and weaknesses of circulating biomarkers for monitoring treatment response.