Pancreatic cancer-associated Cathepsin E as a drug activator.

TitlePancreatic cancer-associated Cathepsin E as a drug activator.
Publication TypeJournal Article
Year of Publication2013
AuthorsAbd-Elgaliel WR, Cruz-Monserrate Z, Wang H, Logsdon CD, Tung C-H
JournalJ Control Release
Volume167
Issue3
Pagination221-7
Date Published2013 May 10
ISSN1873-4995
KeywordsAminolevulinic Acid, Animals, Carcinoma, Pancreatic Ductal, Cathepsin E, Cell Line, Tumor, Humans, Light, Mice, Mice, Transgenic, Pancreatic Neoplasms, Photochemotherapy, Prodrugs
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat, and better means to detect and/or treat pancreatic cancer are urgently needed to save lives. Cathepsin E (Cath E) is a proteolytic enzyme highly expressed in PDAC. In this study, a novel approach using Cath E activation of a Cath E-specific prodrug was demonstrated. Specific activation of the prodrug is expected to kill pancreatic cancer cells without harming normal pancreatic cells. A novel 5-aminolevulinic acid (5-ALA) prodrug was custom-designed to be activated selectively by endogenous Cath E within the PDAC cells. The 5-ALA prodrug was incubated with Cath E-positive and -negative tumor cells and illuminated with various doses of light. In addition, mice genetically engineered to develop PDAC were injected intravenously with the 5-ALA prodrug, and the pancreas was treated with light irradiation. One day after treatment, PDAC tissue was assessed for apoptosis. The 5-ALA prodrug was activated within the Cath E-positive tumor but not in the normal pancreatic tissue. When used in combination with light treatment, it allowed delivery of selective photodynamic therapy (PDT) to the cancerous tissues, with minimal harm to the adjacent normal tissues. With this novel Cath E activation approach, it is possible to detect pancreatic cancer cells accurately and specifically impair their viability, while sparing normal cells. This treatment could result in fewer side effects than the non-specific treatments currently in use. Cath E is a specific and effective drug activator for PDAC treatment.

DOI10.1016/j.jconrel.2013.02.007
Alternate JournalJ Control Release
PubMed ID23422726
PubMed Central IDPMC3638719
Grant ListR01 CA135312 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
CA135312 / CA / NCI NIH HHS / United States
CA16672 / CA / NCI NIH HHS / United States
U54 CA151668 / CA / NCI NIH HHS / United States
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065