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1 December 2014
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Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the synthesis of polyamines, and it is overexpressed in a variety of cancers, including pancreatic cancer. Activation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses. Longitudinal profiling of tumor progression revealed that ODC and polyamine synthesis levels were increased in KrasG12D-activated genetically engineered mice and correlated with aggressiveness of tumor growth. The ODC inhibitor, eflornithine (DFMO), caused modulation of ODC pathway signaling with significant inhibition of pancreatic ductal adenocarcinoma (PDAC) incidence, tumor cell proliferation, and increased expression of p21/p27 in KrasG12D mice. These preclinical data indicate that DFMO applied at clinically relevant dose levels has potential for chemoprevention of pancreatic cancer. The figure depicts immunofluorescence staining of pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC showing membranous and cytoplasmic localization of ODC (green). Counter nuclei staining was performed with DAPI (blue). See the article by Mohammed and colleagues (beginning on page 1198) for more information. - PDF Icon PDF LinkTable of Contents
ISSN 1940-6207
EISSN 1940-6215
Issue Sections
Perspective
Research Articles
Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling
Altaf Mohammed; Naveena B. Janakiram; Venkateshwar Madka; Rebekah L. Ritchie; Misty Brewer; Laura Biddick; Jagan Mohan R. Patlolla; Michael Sadeghi; Stan Lightfoot; Vernon E. Steele; Chinthalapally V. Rao
A DRD1 Polymorphism Predisposes to Lung Cancer among Those Exposed to Secondhand Smoke during Childhood
Ana I. Robles; Ping Yang; Jin Jen; Andrew C. McClary; Kara Calhoun; Elise D. Bowman; Kirsi Vähäkangas; K. Leigh Greathouse; Yi Wang; Susan Olivo-Marston; Angela S. Wenzlaff; Bo Deng; Ann G. Schwartz; Bríd M. Ryan
Proton Pump Inhibitors and Histamine 2 Blockers Are Associated with Improved Overall Survival in Patients with Head and Neck Squamous Carcinoma
Silvana Papagerakis; Emily Bellile; Lisa A. Peterson; Maria Pliakas; Katherine Balaskas; Sara Selman; David Hanauer; Jeremy M.G. Taylor; Sonia Duffy; Gregory Wolf
Acknowledgment to Reviewers
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