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Do anti-stroma therapies improve extrinsic resistance to increase the efficacy of gemcitabine in pancreatic cancer?

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies, with approximately 20–30% of PDAC patients receiving the surgical resection with curative intent. Although many studies have focused on finding ideal “drug chaperones” that facilitate and/or potentiate the effects of gemcitabine (GEM) in pancreatic cancer, a significant benefit in overall survival could not be demonstrated for any of these combination therapies in PDAC. Given that pancreatic cancer is characterized by desmoplasia and the dual biological roles of stroma in pancreatic cancer, we reassess the importance of stroma in GEM-based therapeutic approaches in light of current findings. This review is focused on understanding the role of stromal components in the extrinsic resistance to GEM and whether anti-stroma therapies have a positive effect on the GEM delivery. This work contributes to the development of novel and promising combination GEM-based regimens that have achieved significant survival benefits for the patients with pancreatic cancer.

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Acknowledgements

This study was jointly funded by the National Science Foundation for Distinguished Young Scholars of China (No. 81625016), the National Natural Science Foundation of China (No. 81372651, 81502031) and the Shanghai Sailing Program (No. 17YF1402500).

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  1. Chen Liang, Si Shi and Qingcai Meng contributed equally to this work.

Authors and Affiliations

  1. Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People’s Republic of China

    Chen Liang, Si Shi, Qingcai Meng, Dingkong Liang, Shunrong Ji, Bo Zhang, Yi Qin, Jin Xu, Quanxing Ni & Xianjun Yu

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China

    Chen Liang, Si Shi, Qingcai Meng, Dingkong Liang, Shunrong Ji, Bo Zhang, Yi Qin, Jin Xu, Quanxing Ni & Xianjun Yu

  3. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, People’s Republic of China

    Chen Liang, Si Shi, Qingcai Meng, Dingkong Liang, Shunrong Ji, Bo Zhang, Yi Qin, Jin Xu, Quanxing Ni & Xianjun Yu

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Liang, C., Shi, S., Meng, Q. et al. Do anti-stroma therapies improve extrinsic resistance to increase the efficacy of gemcitabine in pancreatic cancer?. Cell. Mol. Life Sci. 75, 1001–1012 (2018). https://doi.org/10.1007/s00018-017-2678-7

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