Early cancer detection can lead to dramatically improved effectiveness of treatment strategies. Blood-based diagnosis would be a major advantage in this regard, but despite intensive research efforts over decades, many apparently promising blood biomarkers have failed clinically. Problems such as variability of cancer biomarker expression by non-malignant cells and heterogeneity among tumours have proved to be frustratingly intractable.
In the current study, the research team attempted to overcome these issues by artificially engineering the tumour cells to express a reporter which is not normally expressed in any tissue. The researchers used nonviral safe vectors called “tumor-activatable minicircles”. These used the pan-tumour–specific survivin promoter to drive expression of a secretable reporter. The minicircles were systemically administered to mice that were expressing human melanoma metastases and also to tumour-free mice. The results indicated that by measuring blood reporter levels, tumour-bearing mice could be reliably distinguished from tumour-free mice for up to two weeks. Furthermore, tumour burden in the lungs correlated with cumulative reporter levels, indicating that the extent of disease progression could also be determined.
The study authors suggested that their test could first be used in patients with a high risk for tumour recurrence, then for diagnostic screening of high-risk populations and, if proven safe and effective, for the general population. They concluded: “Our system represents an alternative paradigm for improved cancer detection and could enable more timely interventions to combat this devastating disease.”
Reference: Ronald JA, Chuang H-Y, Dragulescu-Andrasi A, Hori SS, Gambhir SS. Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker. PNAS (2015) doi: 10.1073/pnas.1414156112