Pancreatic cancer: are more chemotherapy and surgery needed?

Deplanque, Gaël; Demartines, Nicolas

doi:10.1016/s0140-6736(17)30126-5

Cited by 42 publications

(32 citation statements)

References 9 publications

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“…The major challenge responsible for this poor prognosis is the extreme chemoresistance phenotype of the tumor. The currently available treatment for pancreatic cancer is cytoreductive surgery, followed by gemcitabine-based chemotherapy, which leads to a slight improvement in overall survival 4 - 6 . However, most patients with pancreatic cancer still remain refractory and undergo tumor relapse, ultimately succumbing to this malignant tumor 7 .…”

Section: Introductionmentioning

confidence: 99%

Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway

Yu¹,

Chen²,

Guo³

et al. 2018

Theranostics

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Background: Drug resistance is well known as a major obstacle for cancer recurrence and treatment failure, leading to poor survival in pancreatic cancer, which is a highly aggressive tumor. Identifying effective strategies to overcome drug resistance would have a significant clinical impact for patients with pancreatic cancer.Methods: The protein and mRNA expression of TRIM31 in pancreatic cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. 89 human pancreatic cancer tissue samples were analyzed by IHC to investigate the association between TRIM31 expression and the clinicopathological characteristics of pancreatic cancer patients. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of TRIM31 in human pancreatic cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM31 promotes chemoresistance in pancreatic cancer cells.Results: The expression of TRIM31was markedly upregulated in pancreatic cancer cell lines and tissues, and high TRIM31 expression was associated with an aggressive phenotype and poor prognosis with pancreatic cancer patients. TRIM31 overexpression confers gemcitabine resistance on pancreatic cancer cells; however, inhibition of TRIM31 sensitized pancreatic cancer cell lines to gemcitabine cytotoxicity both in vitro and in vivo. Additionally, TRIM31 upregulated the levels of nuclear p65 by promoting K63-linked polyubiquitination of tumor necrosis factor receptor-associated factor 2 (TRAF2) and sustained the activation of nuclear transcription factor kappa B (NF-κB) in pancreatic cancer cells.Conclusions: Our findings provided evidence that TRIM31 is a potential therapeutic target for patients with pancreatic cancer. Targeting TRIM31 signaling may be a promising strategy to enhance gemcitabine response during pancreatic cancer chemo-resistance.

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Section: Introductionmentioning

confidence: 99%

Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway

Yu¹,

Chen²,

Guo³

et al. 2018

Theranostics

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show abstract

“…Even for patients with early stage disease, intrahepatic metastases were frequently occurred after curative resection 5 - 7 . In contrast, traditional chemotherapy and targeted therapy has been unsatisfactory in treatment of metastatic pancreatic cancer so far 8 , 9 . Though clinical approaches, such as imaging, pathology and serum tumor markers were widely used to monitor disease progression currently, detection and assessment of early intrahepatic metastases are still challenging for pancreatic cancer 3 .…”

Section: Introductionmentioning

confidence: 99%

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

Liu

et al. 2018

J. Cancer

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Pancreatic cancer is amongst the most lethal malignancies with increasing incidence and mortality worldwide. Distant metastases, especially intrahepatic metastases, is the leading cause of death for pancreatic cancer. Circulating tumor cells (CTCs) are neoplastic cells released from the primary tumor into circulation, and play critical roles in metastases of various types of cancers. Though clinical studies showed that detection of CTCs in peripheral circulation was associated with worse prognosis in patients with breast cancer and hepatocellular carcinoma, detection CTCs in peripheral blood of pancreatic cancer was still challenging due to hepatic filtration and technical limitations. Previous studies have demonstrated that CTCs could be detected in portal vein circulation in patients with pancreaticobiliary carcinoma. In the present study, taking advantage of ultrasonography-guided transhepatic puncture, we analysis CTCs in portal vein blood obtained from patients with advanced pancreatic cancer. CTCs were detected in all 29-portal vein blood of samples, and absolute numbers of circulating pancreatic cancer cells in portal vein was significantly higher than that in peripheral circulation. Furthermore, we found that CTC counts in portal vein was highly associated with intrahepatic metastases and indicated poorer prognosis in patients with advanced pancreatic cancer. Short-term expansion and in vitro drug sensitivity assay showed that CTCs derived from portal vein blood were highly resistant to several chemotherapy regimens. In summary, detection of CTCs in portal vein could be a powerful tool to stratify the risk of intrahepatic metastases of pancreatic cancer, and provided new insight into the biological feature of pancreatic cancer metastases and drug resistance.

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“…However, the majority of patients are diagnosed at an advanced stage of pancreatic cancer. Recently, clinical trials examining chemotherapy to cure pancreatic cancer have been undertaken to identify a more effective method with which to prolong the life expectancy of patients; however, the long-term curative effects and better choices of different chemotherapeutic combinations remain uncertain ( 1 – 3 ). Moreover, early metastasis is another non-negligible cause of a poor outcome for patients with pancreatic cancer ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer

Huang

Chen

et al. 2018

Int J Oncol

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Alterations in Wiskott-Aldrich syndrome protein family verprolinhomologous protein 3 (WAVE3) expression play various roles in certain types of cancer. However, the roles of WAVE3 expression in pancreatic cancer remain unknown. The present retrospective study demonstrated that WAVE3 expression was higher in cancerous pancreatic tissues than in non-neoplastic tissues. Moreover, WAVE3 overexpression was related to lymphatic metastasis, a poor differentiation and high pre-operative CA19-9 levels and was an adverse prognostic factor for patients with pancreatic cancer. In vitro, the knockdown of WAVE3 inhibited the proliferative, migratory and invasive potential of pancreatic cancer cells and promoted cell apoptosis. Western blot analysis demonstrated that WAVE3 influenced the protein kinase B (PBK/AKT) pathway by suppressing the expression of pyruvate dehydrogenase kinase isoform 2 (PDK2) and then negatively inhibiting the phosphorylation of Ser473 on AKT. Furthermore, the expression of AKT pathway downstream proteins [certain epithelial-mesenchymal transition (EMT)-related proteins, p53, Bcl-2 and cyclin D1] was accordingly altered. Taken together, our findings suggest that WAVE3 influences cell proliferation, migration and invasion via the AKT pathway, and targeting WAVE3 and/or the AKT pathway may potentially serve as a treatment strategy for pancreatic cancer.

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Pancreatic cancer: are more chemotherapy and surgery needed?

Cited by 42 publications

References 9 publications

Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway

Oncogenic TRIM31 confers gemcitabine resistance in pancreatic cancer via activating the NF-κB signaling pathway

Detection of CTCs in portal vein was associated with intrahepatic metastases and prognosis in patients with advanced pancreatic cancer

WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer

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