Complex Roles of the Stroma in the Intrinsic Resistance to Gemcitabine in Pancreatic Cancer: Where We Are and Where We Are Going

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2018 Apr 4

PMID 29611542

Citations 73

Authors

Chen Liang

Si Shi

Qingcai Meng

Dingkong Liang

Shunrong Ji

Bo Zhang

Yi Qin

Jin Xu

Quanxing Ni

Xianjun Yu

Affiliations

Soon will be listed here.

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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