Plasma signals of lung tumor promotion and the ubiquitous challenge of biomarker specificity

This opinion paper examines a recently reported 14-biomarker plasma panel designed to predict lung cancer development and identify patients who might benefit from preventive canakinumab treatment. While stratifying patients using this panel and clinical risk factors improves the number needed to treat (NNT) from 1,000 down to 50, the strategy still faces major hurdles due to the high economic cost and systemic side effects of canakinumab, which limits clinical benefit to a tiny fraction of the treated group. A closer biochemical examination reveals that the panel's 14 markers-such as CEACAM5 (CEA) and WFDC2 (HE4)-are already well-documented in classic tumor marker literature and are notoriously non-specific, frequently becoming elevated across various malignancies. Furthermore, notable established markers like CYFRA 21-1 and CA125 are missing from the panel. Ultimately, because these markers lack organ specificity, they are not utilized for early detection. The logical next step for this field will be the development of a single multiplex assay to quantify all 14 proteins simultaneously.