Circulating cancer biomarkers: current status and future prospects

Circulating biomarkers are widely used in the management of patients with cancer, especially in assessing prognosis, surveillance following curative-intent surgery and monitoring therapy. Inadequate sensitivity and specificity, however, limit the use of most existing biomarkers in screening asymptomatic subjects for early malignancy. Currently, only two circulating biomarkers are recommended for cancer screening, that is, prostate-specific antigen for prostate cancer following a process of shared decision-making and alpha-fetoprotein in specific high-risk subjects for hepatocellular cancer. Emerging biomarkers include circulating tumor DNA (ctDNA), micro-RNAs, circulating tumor cells, and extracellular vesicles. Of these, ctDNA is likely to have the biggest clinical impact, especially for early cancer detection/screening and therapy planning. Among the currently approved ctDNA biomarkers are mutant EGFR for predicting response to EGFR inhibitors in advanced nonsmall cell lung cancer, mutant PIK3CA for predicting response to alpelisib in combination with fulvestrant in advanced breast cancer and methyl SEPT9 in screening for early colorectal cancer.