Current knowledge on drug resistance and therapeutic approaches to eliminate pancreatic cancer stem cells

2019 ◽  
pp. 69-80 ◽  
Author(s):  
Astrid Belalcazar ◽  
Ganji Purnachandra Nagaraju
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Pancreatic Cancer Stem Cells

scholarly journals Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210

2019 ◽  
Vol 43 (1) ◽  
pp. 123-136 ◽  
Author(s):  
Zhiyong Yang ◽  
Ning Zhao ◽  
Jing Cui ◽  
Heshui Wu ◽  
Jiongxin Xiong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Expression Levels ◽  
Pancreatic Cancer Cells ◽  
Pancreatic Cancer Stem Cells

Abstract Purpose Gemcitabine (GEM)-based chemotherapy is the first-line treatment for locally advanced pancreatic cancer. GEM resistance, however, remains a significant clinical challenge. Here, we investigated whether exosomes derived from GEM-resistant pancreatic cancer stem cells (CSCs) mediate cell-cell communication between cells that are sensitive or resistant to GEM and, by doing so, regulate drug resistance. Methods GEM-sensitive BxPC-3-derived BxS and PANC-1 pancreatic cancer cells were cultured with exosomes extracted from CSCs isolated from GEM-resistant BxPC-3-derived BxR cells (BxR-CSC). The effect of exosomes on drug resistance, cell cycle progression, apoptosis and miRNA expression was evaluated in BxS and PANC-1 cells. Relevant miRNAs associated with GEM resistance were identified and the role of miR-210 in conferring drug resistance was examined in vitro and in vivo. Results BxR-CSC-derived exosomes induced GEM resistance, inhibited GEM-induced cell cycle arrest, antagonized GEM-induced apoptosis, and promoted tube formation and cell migration in BxS and PANC-1 cells. Elevated miR-210 expression levels were detected in BxR-CSCs and BxR-CSC-derived exosomes compared to those in BxS-CSCs and BxS-CSC-derived exosomes. In addition, increased expression levels of miR-210 were observed in BxS and PANC-1 cells cultured with BxR-CSC-derived exosomes upon exposure to GEM in a dose-dependent manner. Also, a series of biological changes was observed in BxS cells after transfection with miR-210 mimics, including activation of the mammalian target of rapamycin (mTOR) signaling pathway, and these changes were similar to those triggered by BxR-CSC-derived exosomes. Conclusions Our findings suggest that exosomes derived from GEM-resistant pancreatic cancer stem cells mediate the horizontal transfer of drug-resistant traits to GEM-sensitive pancreatic cancer cells by delivering miR-210.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Sabrina Bimonte ◽  
Antonio Barbieri ◽  
Maddalena Leongito ◽  
Giuseppe Palma ◽  
Vitale del Vecchio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Biological Activities ◽  
Biological Properties ◽  
Ductal Adenocarcinoma ◽  
Small Noncoding Rnas ◽  
Pancreatic Cancer Stem Cells

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.

scholarly journals Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells

2021 ◽  
Vol 22 (9) ◽  
pp. 4765
Author(s):  
Susmita Barman ◽  
Iram Fatima ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Therapeutic Approaches ◽  
Cancer Types ◽  
Pancreatic Cancer Stem Cells

Despite significant improvements in clinical management, pancreatic cancer (PC) remains one of the deadliest cancer types, as it is prone to late detection with extreme metastatic properties. The recent findings that pancreatic cancer stem cells (PaCSCs) contribute to the tumorigenesis, progression, and chemoresistance have offered significant insight into the cancer malignancy and development of precise therapies. However, the heterogeneity of cancer and signaling pathways that regulate PC have posed limitations in the effective targeting of the PaCSCs. In this regard, the role for K-RAS, TP53, Transforming Growth Factor-β, hedgehog, Wnt and Notch and other signaling pathways in PC progression is well documented. In this review, we discuss the role of PaCSCs, the underlying molecular and signaling pathways that help promote pancreatic cancer development and metastasis with a specific focus on the regulation of PaCSCs. We also discuss the therapeutic approaches that target different PaCSCs, intricate mechanisms, and therapeutic opportunities to eliminate heterogeneous PaCSCs populations in pancreatic cancer.

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