Mathematical framework for activity-based cancer biomarkers
Gabriel A. Kwong, Jaideep S. Dudani, Emmanuel Carrodeguas, Eric V. Mazumdar, Seyedeh M. Zekavat, Sangeeta N. Bhatia
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Published: Sep 28, 2015
DOI: 10.1073/pnas.1506925112
Open original source ↗Source abstract
Significance The discovery of cancer at an early stage improves treatment outcomes, yet cancer detection thresholds based on measuring the abundance of biomarkers produced by small tumors are biologically limited. Here we develop a mathematical framework to explore the use of activity-based biomarkers for early cancer detection. In contrast to abundance-based biomarkers, activity-based biomarkers rely on the catalytic activity of enzymes to amplify cancer-derived signals and allow detection of small tumors. Using a class of activity-based biomarkers called synthetic biomarkers, we comprehensively explore how detection sensitivities depend on probe design, enzymatic activity, and organ physiology, and how they may be precisely tuned to reveal the presence of small tumors in humans.
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