Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling Journal Article

Authors: Kirkpatrick, J. D.; Warren, A. D.; Soleimany, A. P.; Westcott, P. M. K.; Voog, J. C.; Martin-Alonso, C.; Fleming, H. E.; Tammela, T.; Jacks, T.; Bhatia, S. N.
Article Title: Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling
Abstract: Lung cancer is the leading cause of cancer-related death, and patients most commonly present with incurable advanced-stage disease. U.S. national guidelines recommend screening for high-risk patients with low-dose computed tomography, but this approach has limitations including high false-positive rates. Activity-based nanosensors can detect dysregulated proteases in vivo and release a reporter to provide a urinary readout of disease activity. Here, we demonstrate the translational potential of activity-based nanosensors for lung cancer by coupling nanosensor multiplexing with intrapulmonary delivery and machine learning to detect localized disease in two immunocompetent genetically engineered mouse models. The design of our multiplexed panel of sensors was informed by comparative transcriptomic analysis of human and mouse lung adenocarcinoma datasets and in vitro cleavage assays with recombinant candidate proteases. Intrapulmonary administration of the nanosensors to a Kras- and Trp53-mutant lung adenocarcinoma mouse model confirmed the role of metalloproteases in lung cancer and enabled accurate detection of localized disease, with 100% specificity and 81% sensitivity. Furthermore, this approach generalized to an alternative autochthonous model of lung adenocarcinoma, where it detected cancer with 100% specificity and 95% sensitivity and was not confounded by lipopolysaccharide-driven lung inflammation. These results encourage the clinical development of activity-based nanosensors for the detection of lung cancer. Copyright © 2020 The Authors
Journal Title: Science Translational Medicine
Volume: 12
Issue: 537
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2020-04-01
Start Page: eaaw0262
Language: English
DOI: 10.1126/scitranslmed.aaw0262
PUBMED: 32238573
PROVIDER: scopus
Notes: Article -- Export Date: 1 May 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Justin Voog
    1 Voog