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Proteolysis activity mapping and substrate discovery platform for identifying tumor-activated biosensors
Itay Algov1,2, Audrey Van Heest3,4, Megan Hopton4,5
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature Chemical Biology
|May 11, 2026
Summary
Researchers developed PSurf, a new platform for discovering cancer-specific protease sensors. This technology enables precise, non-invasive tumor detection by identifying activated probes in tissue samples.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Dysregulated extracellular proteolytic activity is a key feature of cancer.
- Current methods lack the ability to screen proteolytic events directly in specific tissue samples, hindering probe discovery.
Purpose of the Study:
- To develop a platform (PSurf) for identifying tissue-specific protease sensors.
- To enable the discovery of tumor-activated probes for precise cancer detection.
Main Methods:
- PSurf platform utilizes differential selection of tumor-specific sequences over healthy tissue.
- Engineered nanobody-targeted biosensors release urinary reporters upon tumor-specific cleavage.
- Validated in a mouse lung metastasis model for non-invasive tumor detection.
Main Results:
- PSurf successfully identified context-specific, tumor-activated probes.
- These probes precisely distinguished metastatic lesions in lung tissue slices.
- Developed biosensors enabled precise non-invasive tumor detection in vivo.
Conclusions:
- PSurf provides a novel method for discovering tissue-specific protease sensors.
- This platform facilitates the development of conditionally activated agents for cancer detection and therapy.
- Enables precise mapping of tissue-specific protease activity for probe discovery.
