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Review
. 2016 Mar;6(2):101-5.
doi: 10.1016/j.apsb.2016.01.002. Epub 2016 Jan 21.

Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma

Norihiro Sato  1 , Xiao-Bo Cheng  1 , Shiro Kohi  1 , Atsuhiro Koga  1 , Keiji Hirata  1
Affiliations
Review

Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma

Norihiro Sato et al. Acta Pharm Sin B. 2016 Mar.

Abstract

Progression of cancer is often associated with interactions between cancer cells and extracellular matrix (ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan (HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.

Keywords: 4-Methylumbelliferone; Desmoplasia; Hyaluronan; PEGPH20; Pancreatic ductal    adenocarcinoma; Therapeutic target; Tumor stroma; Tumor–stromal    interaction.

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Figures

fx1
Graphical abstract
Fig. 1
Figure 1
Overexpression of hyaluronan in human pancreatic ductal adenocarcinoma tissue by immunohistochemical staining. Strong staining is observed mainly in tumor cells (arrows) but is also present in stroma (⁎).
Fig. 2
Figure 2
Strategies of targeting hyaluronan for the treatment of pancreatic cancer. Currently, three different therapeutic approaches may are considered: (1) inhibiting HA synthesis, (2) blocking HA signaling, and (3) depleting stromal HA barrier in PDAC to improve chemosensitivity.
See this image and copyright information in PMC

References

    1. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. - PubMed
    1. Sato N., Goggins M. The role of epigenetic alterations in pancreatic cancer. J Hepatobiliary Pancreat Surg. 2006;13:286–295. - PubMed
    1. Vincent A., Herman J., Schulick R., Hruban R.H., Goggins M. Pancreatic cancer. Lancet. 2011;378:607–620. - PMC - PubMed
    1. Rowe R.G., Weiss S.J. Navigating ECM barriers at the invasive front: the cancer cell–stroma interface. Annu Rev Cell Dev Biol. 2009;25:567–595. - PubMed
    1. Toole B.P. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004;4:528–539. - PubMed

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