2016
DOI: 10.1158/1535-7163.mct-15-0774
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Expression of GRP78, Master Regulator of the Unfolded Protein Response, Increases Chemoresistance in Pancreatic Ductal Adenocarcinoma

Abstract: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is dismal. Although gemcitabine (GEM) is the standard chemotherapeutic agent for adjuvant therapy of resectable PDAC, recurrent disease is observed in an alarming number of GEM-treated patients. Regardless of the adjuvant therapy, the vast majority of patients treated with chemotherapy after surgical resection show tumor recurrence. A better understanding of the molecular mechanisms that contribute to chemoresistance would aid the developm… Show more

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Cited by 88 publications
(72 citation statements)
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“…Additionally, we found GRP78 to be overexpressed in the ducts/pseudoducts of patient biopsy punches, which is consistent with recently published studies (Fig. 1E) (Gifford et al ., 2016; Niu et al ., 2015). …”
Section: Resultsmentioning
confidence: 99%
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“…Additionally, we found GRP78 to be overexpressed in the ducts/pseudoducts of patient biopsy punches, which is consistent with recently published studies (Fig. 1E) (Gifford et al ., 2016; Niu et al ., 2015). …”
Section: Resultsmentioning
confidence: 99%
“…GRP78, one of the regulators of the UPR, is an attractive target because it is responsible for maintaining homeostasis in the ER. Recently, a small molecule GRP78 inhibitor called IT‐139 was shown to sensitize chemoresistant PDAC cells to gemcitabine (Gifford et al ., 2016). Our previously published data shows that GRP78‐mediated ER homeostasis is dependent on SP1 activity and inhibition of SP1 prevents the homeostasis and pushes the UPR to a chronic ER stress phase, leading to cancer cell death (Dauer et al ., 2017).…”
Section: Discussionmentioning
confidence: 99%
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