Renalase (RNLS) is a secreted flavoprotein. It is over-expressed by pancreatic cancer and acts as a survival factor blocking apoptosis. Importantly RNLS activates STAT3 and establishes a positive feedback loop whereby STAT3 promotes greater RNLS expression .
STAT3 plays a major role in pancreatic cancer . It will be very important to determine through further research the extent to which STAT3 mediates renalase’s pro-cancer effects. A combination of renalase and STAT3 inhibition may prove effective against pancreatic cancer. A STAT3 inhibitor is already in clinical trials .
As renalase is secreted it may also serve as a useful diagnostic blood biomarker of pancreatic cancer (See here for pancreatic cancer biomarkers under development). This is certainly worth pursuing as late detection is a major reason for the dismal outcomes of pancreatic cancer patients.
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- Corcoran, R. B., G. Contino, V. Deshpande, A. Tzatsos, C. Conrad, C. H. Benes, D. E. Levy, J. Settleman, J. A. Engelman, and N. Bardeesy. ‘STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis’. Cancer Research 71, no. 14 (15 July 2011): 5020–29. doi:10.1158/0008-5472.CAN-11-0908.
- Hong, David, Razelle Kurzrock, Youngsoo Kim, Richard Woessner, Anas Younes, John Nemunaitis, Nathan Fowler, et al. ‘AZD9150, a next-Generation Antisense Oligonucleotide Inhibitor of STAT3 with Early Evidence of Clinical Activity in Lymphoma and Lung Cancer’. Science Translational Medicine 7, no. 314 (18 November 2015): 314ra185. doi:10.1126/scitranslmed.aac5272.