Abstract:
:Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemotherapy- and radiotherapy-resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has shown promising results in preclinical studies; however, the benefits were not readily translated into clinical trials with PDAC patients. In this study, utilizing mouse models of PDAC, we showed that inhibition of either HGF/c-Met or Hh pathways sensitize the PDAC tumors to gemcitabine, resulting in decreased primary tumor volume as well as significant reduction of metastatic tumor burden. However, prolonged treatment of single HGF/c-Met or Hh inhibitor leads to resistance to these single inhibitors, likely because the single c-Met treatment leads to enhanced expression of Shh, and vice versa. Targeting both the HGF/c-Met and Hh pathways simultaneously overcame the resistance to the single-inhibitor treatment and led to a more potent antitumor effect in combination with the chemotherapy treatment. Mol Cancer Ther; 16(11); 2399-409. ©2017 AACR.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Rucki AA,Xiao Q,Muth S,Chen J,Che X,Kleponis J,Sharma R,Anders RA,Jaffee EM,Zheng Ldoi
10.1158/1535-7163.MCT-16-0452subject
Has Abstractpub_date
2017-11-01 00:00:00pages
2399-2409issue
11eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-16-0452journal_volume
16pub_type
杂志文章abstract::Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of ATP-sensitive potassium channels (KATP channels) and the receptor of antidiabetic drugs, such as glibenclamide, which induce insulin secretion in pancreatic β cells. However, the expression and role of SUR1 in cancer are unknown. In this study, we found that ...
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journal_title:Molecular cancer therapeutics
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doi:10.1158/1535-7163.MCT-08-0183
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0424
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0867
更新日期:2014-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
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doi:
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doi:10.1158/1535-7163.MCT-07-2429
更新日期:2008-06-01 00:00:00
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doi:10.1158/1535-7163.MCT-17-0032
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journal_title:Molecular cancer therapeutics
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doi:
更新日期:2003-10-01 00:00:00
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更新日期:2018-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0135
更新日期:2014-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
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