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Pirfenidone normalizes the tumor microenvironment to improve chemotherapy.


ABSTRACT: Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization. Using two orthotopic mammary tumor models we demonstrate that Pirfenidone reduces collagen and hyaluronan levels and, as a result, significantly increases blood vessel functionality and perfusion and improves the anti-tumor efficacy of doxorubicin. Reduction of extracellular matrix components were mediated via TGF? signaling pathway inhibition due to downregulation of TGF?1, COL1A1, COL3A1, HAS2, HAS3 expression levels. Our findings provide evidence that repurposing Pirfenidone could be used as a promising strategy to enhance drug delivery to solid tumors by normalizing the tumor microenvironment.

SUBMITTER: Polydorou C 

PROVIDER: S-EPMC5421866 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Pirfenidone normalizes the tumor microenvironment to improve chemotherapy.

Polydorou Christiana C   Mpekris Fotios F   Papageorgis Panagiotis P   Voutouri Chrysovalantis C   Stylianopoulos Triantafyllos T  

Oncotarget 20170401 15


Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidon  ...[more]

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