Mathematical model for synthetic cancer biomarkers

Mathematical model for synthetic cancer biomarkers

Cancer treatment outcomes improve when the disease is detected early. However, abundance-based biomarkers produced by small tumors circulate for only short periods in blood, are diluted, and vary widely in magnitude. Thus, tumors may reach 1–2 cm in diameter and remain undetectable with blood biomarkers.

Researchers developed a mathematical model that can reveal nonintuitive behaviors of activity-based biomarkers, or probes, which provide an alternative to blood biomarkers.

Using activity-based probes called synthetic biomarkers, which consist of nanoparticles conjugated with protease-cleavable peptides, cancer-related signals can be generated when peptides are cleaved by tumor proteases and concentrated in urine.

Building on previous work on engineering synthetic biomarkers, the authors used polyethylene glycol cores to explore enzyme kinetics, dosage, organ physiology, and probe stability in a mouse model of colorectal cancer with the goal of identifying the parameters that may increase detection sensitivity. 

The model predicts that activity-based probes may be able to elevate signals from tumors as small as 5 mm in diameter to levels detectable in urine by a common diagnostic technique called ELISA.

The model can be expanded to include multiple proteases and their inhibitors, according to the authors.