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Review
. 2017 Dec 1;49(12):e406.
doi: 10.1038/emm.2017.255.

Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going

Chen Liang  1   2   3 , Si Shi  1   2   3 , Qingcai Meng  1   2   3 , Dingkong Liang  1   2   3 , Shunrong Ji  1   2   3 , Bo Zhang  1   2   3 , Yi Qin  1   2   3 , Jin Xu  1   2   3 , Quanxing Ni  1   2   3 , Xianjun Yu  1   2   3
Affiliations
Review

Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going

Chen Liang et al. Exp Mol Med. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The intrinsic and extrinsic mechanisms of gemcitabine (GEM) resistance. Intrinsic resistance refers to modification of transport mechanisms and the metabolism of the drug and activation of intracellular antiapoptosis pathways. Extrinsic resistance is primarily due to impairment of drug delivery.
See this image and copyright information in PMC

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