Harnessing protease activity to improve cancer care
Author(s)Dudani, Jaideep S.; Warren, Andrew D.; Bhatia, Sangeeta N.
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Proteolysis plays critical roles in normal and pathologic physiology; these enzymes are intricately involved in cancer progression and spread. Our understanding of protease function has advanced from nonspecific degrading enzymes to a modern appreciation of their diverse roles in posttranslational modification and signaling in a complex microenvironment. This new understanding has led to next-generation diagnostics and therapeutics that exploit protease activity in cancer. For diagnostics, protease activity may be measured as a biomarker of cancer, with wide-ranging utility from early detection to monitoring therapeutic response. Therapeutically, while broad inhibition of protease activity proved disappointing, new approaches that more specifically modulate proteases in concert with secondary targets might enable potent combination therapies. In addition, clinical evaluation is underway for tools that leverage protease activity to activate therapeutics, ranging from imaging agents that monitor surgical margins to immunotherapies with improved specificity. Technologies that interact with, measure, or modulate proteases are poised to improve cancer management on diagnostic and therapeutic fronts to realize the promise of precision medicine. ©2018 Keywords: protease activity; degradomics; activity-based biomarkers; responsive nanomaterials; protease-targeted therapeutics; protease-triggered therapeutics
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology
Annual review of cancer biology
Dudani, Jaideep S., Andrew D. Warren, and Sangeeta N. Bhatia, "Harnessing protease activity to improve cancer care." Annual review of cancer biology 2 (2018): p. 353-76 doi 10.1146/ANNUREV-CANCERBIO-030617-050549 ©2018 Author(s)
Author's final manuscript