Gemcitabine-resistant pancreatic cancer: a second-line option

Oettle, Helmut; Lehmann, Thorsten G.

doi:10.1016/s0140-6736(15)01035-1

Cited by 13 publications

(11 citation statements)

References 8 publications

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“…It has been reported that GEM resistance is common in primary or acquired pancreatic cancers . Considering that GEM is a basic therapy, several studies have explored the underlying mechanism of GEM resistance .…”

Section: Discussionmentioning

confidence: 99%

“…Gemcitabine (GEM) is as standard therapeutic for pancreatic cancer for many years . However, there is common resistance toward GEM for primary or acquired reasons, and many studies have been evaluating GEM resistance in pancreatic cancer . To elevate GEM‐based treatment, biomarkers were used, including CA19‐9, deoxycytidine kinase, and microRNA; however, these biomarkers have been demonstrated to be insufficient .…”

Section: Introductionmentioning

confidence: 99%

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Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

Fan

et al. 2019

Cancer Medicine

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Gemcitabine (GEM) is the standard chemotherapy drug for pancreatic cancer. Because of widespread drug resistance, the effect is limited. Therefore, it is urgent to reveal the underlying mechanism. Glycolysis is the most remarkable character of tumor aberrant metabolism, which plays vital roles on tumor drug resistance. Hexokinase 2 (HK2), as the key enzyme regulating the first‐step reaction of glycolysis, is overexpressed in many kinds of tumors. The putative role of HK2 resisting GEM therapy was investigated in this study. We found that HK2 was overexpressed in pancreatic cancer and associated with poor prognosis. HK2 knockdown decreased pancreatic cancer cell proliferation, migration viability, and promoted cell apoptosis in vitro. HK2 high expression in pancreatic cancer showed GEM resistance. HK2 knockdown increased the sensitivity of pancreatic cancer cell to GEM, the growth of xenograft tumor with HK2 knockdown was also further decreased with the GEM treatment compared with control in vivo. GEM‐resistant pancreatic cancer showed the increase of HK2 dimer rather than HK2 mRNA or protein. Our study revealed that the ROS derived from GEM promoted HK2 dimerization combining with voltage‐dependent anion channel, which resulted in the resistance to GEM. Meanwhile, our study established a new sight for GEM resistance in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

Fan

et al. 2019

Cancer Medicine

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“…The development of chemotherapy resistance is a complex process that involves multifactors, multiple genes, and multiple mechanisms. Increasing the sensitivity of chemotherapy has been one of the hotspots in PC research (5)(6)(7). At present, existing studies have shown that changes in the related genes, tumor microenvironment, cellular signaling pathways, and regulation of autophagy are the main causes for the development of chemotherapy resistance.…”

Section: Introductionmentioning

confidence: 99%

Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy

et al. 2021

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Chemotherapy is crucial for the treatment of pancreatic cancer (PC). Gemcitabine (GEM) as the first-line chemotherapy drug has a high resistance rate. Increasing the sensitivity of gemcitabine is currently the objectives and challenges of this study. Our previous study showed Girdin was closely related to the progression and prognosis of PC, indicating that Girdin may be associated with chemosensitivity. In the current study, we use recombinant adenovirus to specifically knockdown Girdin in PC cell lines to determine the effect of Girdin in the process of gemcitabine chemosensitivity. Autophagy is one of the pathways affecting the gemcitabine chemosensitivity in PC. Further research validated that Girdin may activate autophagy by interacting with autophagy protein p62/SQSTM1, which could enhance chemotherapy resistance to gemcitabine in PC. Down-regulation of Girdin may therefore increase gemcitabine chemosensitivity in PC. Our results reveal that Girdin acted as a negative regulator of gemcitabine chemosensitivity in PC. Increased autophagy activity caused by abnormally high Girdin expression may be one of the main factors for the reduction in chemosensitivity, which may provide new perspectives on understanding chemosensitization in PC.

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“…PDAC leads to an aggressive local invasion and early metastases, and it is noted that this disease is poorly responsive to treatment with chemotherapy or radiation therapy [ 5 – 7 ]. To date, gemcitabine is the best chemotherapeutic agent used for pancreatic cancer treatment, although patients showed drug resistance over the time [ 8 – 11 ]. In order to improve PDAC prognosis and to bypass the problem of pancreatic tumor chemoresistance, many alternative treatments have been proposed [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of miRNAs in the Regulation of Pancreatic Cancer Stem Cells

Bimonte

Barbieri

Leongito

et al. 2016

Stem Cells International

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Pancreatic ductal adenocarcinoma is currently one of the deadliest cancers with low overall survival rate. This disease leads to an aggressive local invasion and early metastases and is poorly responsive to treatment with chemotherapy or chemoradiotherapy. Several studies have shown that pancreatic cancer stem cells (PCSCs) play different roles in the regulation of drug resistance and recurrence in pancreatic cancer. MicroRNA (miRNA), a class of newly emerging small noncoding RNAs, is involved in the modulation of several biological activities ranging from invasion to metastases development, as well as drug resistance of pancreatic cancer. In this review, we synthesize the latest findings on the role of miRNAs in regulating different biological properties of pancreatic cancer stem cells.

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Gemcitabine-resistant pancreatic cancer: a second-line option

Cited by 13 publications

References 8 publications

Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

Girdin Knockdown Increases Gemcitabine Chemosensitivity to Pancreatic Cancer by Modulating Autophagy

The Role of miRNAs in the Regulation of Pancreatic Cancer Stem Cells

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