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Title: The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer
Author: Martínez-Bosch, Neus
Guerrero, Pedro Enrique.
Moreno, Mireia
José, Anabel
Iglesias, Mar
Munné-Collado, Jessica
Anta, Héctor
Gibert, Joan
Orozco, Carlos Alberto
Vinaixa, Judith
Fillat i Fonts, Cristina
Viñals Canals, Francesc
Navarro, Pilar
Keywords: Càncer de pàncrees
Pancreas cancer
Issue Date: 21-Jun-2016
Publisher: Impact Journals
Abstract: Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2016, vol. 7, num. 30, p. 48265-48279
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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