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Review Article | Open Access

Promising molecular mechanisms responsible for gemcitabine resistance in cancer

Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China
Division of Hematology and Oncology, Department of Pediatrics, Wells Center for Pediatric Research, Indiana University Simon Cancer Center, Indiana University, Indianapolis, IN 46202, USA

Peer review under responsibility of Chongqing Medical University.

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Abstract

Gemcitabine is the first-line treatment for pancreatic ductual adenocarcinoma (PDAC) as well as acts against a wide range of other solid tumors. Patients usually have a good initial response to gemcitabine-based chemotherapy but would eventually develop resistance. To improve survival and prognosis of cancer patients, better understanding of the mechanisms responsible for gemcitabine resistance and discovery of new therapeutic strategies are in great need. Amounting evidence indicate that the developmental pathways, such as Hedgehog (Hh), Wnt and Notch, become reactivated in gemcitabine-resistant cancer cells. Thus, the strategies for targeting these pathways may sensitize cancer cells to gemcitabine treatment. In this review, we will summarize recent development in this area of research and discuss strategies to overcome gemcitabine resistance. Given the cross-talk between these three developmental signaling pathways, designing clinical trials using a cocktail of inhibitory agents targeting all these pathways may be more effective. Ultimately, our hope is that targeting these developmental pathways may be an effective way to improve the gemcitabine treatment outcome in cancer patients.

Keywords

Cancer therapyHedgehogNotchWntGemcitabine resistance

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Genes & Diseases
Volume 2 Issue 4,
December 2015
Pages 299-306
DOI: 10.1016/j.gendis.2015.07.003
Cite this article:
Jia Y, Xie J. Promising molecular mechanisms responsible for gemcitabine resistance in cancer. Genes & Diseases, 2015, 2(4): 299-306. https://doi.org/10.1016/j.gendis.2015.07.003

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Received: 14 June 2015
Accepted: 20 July 2015
Published: 30 July 2015
© 2015, Chongqing Medical University

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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