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Pancreatic Cancer treatment by calcipotriol (a synthetic vitamin D) improves outcome by 57 percent – Sept 2014

Vitamin D Receptor-Mediated Stromal Reprogramming Suppresses Pancreatitis and Enhances Pancreatic Cancer Therapy

Mara H. Sherman1, Ruth T. Yu1, Dannielle D. Engle2, Ning Ding1, Annette R. Atkins1, Herve Tiriac2, Eric A. Collisson3, Frances Connor4, Terry Van Dyke5, Serguei Kozlov6, Philip Martin6, Tiffany W. Tseng1, David W. Dawson7, Timothy R. Donahue7, Atsushi Masamune8, Tooru Shimosegawa8, Minoti V. Apte9, Jeremy S. Wilson9, Beverly Ng10, 11, Sue Lynn Lau10, 12, 13, Jenny E. Gunton10, 11, 12, 13, Geoffrey M. Wahl1, Tony Hunter14, Jeffrey A. Drebin15, Peter J. O’Dwyer16, Christopher Liddle17, David A. Tuveson2, Michael Downes 1 downes at salk.edu , Ronald M. Evans1, 18,

Publisher wants $31.50 for the PDF – publisher also has a 3 minute low-tech video

VitaminDWiki notes

The TOP articles in Pancreatic Cancer and Vitamin D are listed here:

Highlights

•VDR is a master transcriptional regulator in pancreatic stellate cells
•VDR ligands suppress pancreatitis
•Stromal VDR activation overcomes chemotherapeutic drug resistance
•VDR ligand plus gemcitabine enhances survival in a PDA mouse model

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy.

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