ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mathematical framework for activity-based cancer biomarkers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Article
- Spatial Measurement and Inhibition of Calpain Activity in Traumatic Brain Injury with an Activity-Based Nanotheranostic Platform.ACS nano · 2024Article
- Mathematical modeling of the evolution of resistance and aggressiveness of high-grade serous ovarian cancer from patient CA-125 time series.PLoS computational biology · 2024Article
- Targeting and monitoring ovarian cancer invasion with an RNAi and peptide delivery system.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- An Activity-Based Nanosensor for Minimally-Invasive Measurement of Protease Activity in Traumatic Brain Injury.Advanced functional materials · 2023Article
- Liquid biopsies for early diagnosis of brain tumours:Journal of the Royal Society, Interface · 2022Article
- Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors.Nature biomedical engineering · 2022Article
- Synthetic biomarkers: a twenty-first century path to early cancer detection.Nature reviews. Cancer · 2021Review
- Interfacing Biomaterials with Synthetic T Cell Immunity.Advanced healthcare materials · 2021Review
- A survivin-driven, tumor-activatable minicircle system for prostate cancer theranostics.Molecular therapy oncolytics · 2021Article
- The Tumor Proteolytic Landscape: A Challenging Frontier in Cancer Diagnosis and Therapy.International journal of molecular sciences · 2021Review
- Oncological Ligand-Target Binding Systems and Developmental Approaches for Cancer Theranostics.Molecular biotechnology · 2021Review
- Multicompartment modeling of protein shedding kinetics during vascularized tumor growth.Scientific reports · 2020Article
- Engineering synthetic breath biomarkers for respiratory disease.Nature nanotechnology · 2020Article
- Activity-Based Diagnostics: An Emerging Paradigm for Disease Detection and Monitoring.Trends in molecular medicine · 2020Review
- Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling.Science translational medicine · 2020Article
- An Activity-Based Nanosensor for Traumatic Brain Injury.ACS sensors · 2020Article
- Macrophage Sensors for Early Cancer Detection.Clinical chemistry · 2020Article
- Synthetic immunity by remote control.Theranostics · 2020Review
- MMP-14 (MT1-MMP) Is a Biomarker of Surgical Outcome and a Potential Mediator of Hearing Loss in Patients With Vestibular Schwannomas.Frontiers in cellular neuroscience · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Advances in nanomedicine are providing sophisticated functions to precisely control the behavior of nanoscale drugs and diagnostics. Strategies that coopt protease activity as molecular triggers are increasingly important in nanoparticle design, yet the pharmacokinetics of these systems are challenging to understand without a quantitative framework to reveal nonintuitive associations. We describe a multicompartment mathematical model to predict strategies for ultrasensitive detection of cancer using synthetic biomarkers, a class of activity-based probes that amplify cancer-derived signals into urine as a noninvasive diagnostic. Using a model formulation made of a PEG core conjugated with protease-cleavable peptides, we explore a vast design space and identify guidelines for increasing sensitivity that depend on critical parameters such as enzyme kinetics, dosage, and probe stability. According to this model, synthetic biomarkers that circulate in stealth but then activate at sites of disease have the theoretical capacity to discriminate tumors as small as 5 mm in diameter-a threshold sensitivity that is otherwise challenging for medical imaging and blood biomarkers to achieve. This model may be adapted to describe the behavior of additional activity-based approaches to allow cross-platform comparisons, and to predict allometric scaling across species.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.