The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

Nguyen, Lily; Schilling, Daniela; Dobiasch, Sophie; Raulefs, Susanne; Franco, Marina Santiago; Buschmann, Dominik; Pfaffl, Michael W.; Schmid, Thomas E.; Combs, Stephanie E.

doi:10.3390/cancers12123703

Cited by 16 publications

(13 citation statements)

References 140 publications

(122 reference statements)

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“…Currently, surgery is the best curative pathway for pancreatic cancer. However, because of the invasive metastatic nature of pancreatic cancer, 80% of patients are not eligible for surgery, and now immunotherapy has emerged as an effective modality to treat such patients [2,6]. On the other hand, one of the major issues in radiotherapy (RT) in treating pancreatic cancer is the close proximity of adjacent organs at risk, resulting in treatment doses being limited by significant tissues' toxicities, preventing the dose escalation needed for local control [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Nanotechnology has demonstrated a remarkable capability to overcome these challenges [8][9][10][11][12]. For instance, nanoparticles (NPs) have shown promising results as radiosensitizer agents in radiotherapy and as vectors for targeted-drug delivery in chemotherapy [6][7][8]. Understanding of the TME and its interactions with NPs is critical in reaping the benefits of nanotechnology, particularly in pancreatic cancer where tumor stroma acts as a barrier.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

et al. 2021

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Pancreatic cancer is one of the deadliest types of cancer, with a five-year survival rate of only 10%. Nanotechnology offers a novel perspective to treat such deadly cancers through their incorporation into radiotherapy and chemotherapy. However, the interaction of nanoparticles (NPs) with cancer cells and with other major cell types within the pancreatic tumor microenvironment (TME) is yet to be understood. Therefore, our goal is to shed light on the dynamics of NPs within a TME of pancreatic origin. In addition to cancer cells, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were examined in this study due to their important yet opposite roles of suppressing tumor growth and promoting tumor growth, respectively. Gold nanoparticles were used as the model NP system due to their biocompatibility and physical and chemical proprieties, and their dynamics were studied both quantitatively and qualitatively in vitro and in vivo. The in vitro studies revealed that both cancer cells and CAFs take up 50% more NPs compared to NFs. Most importantly, they all managed to retain 70–80% of NPs over a 24-h time period. Uptake and retention of NPs within an in vivo environment was also consistent with in vitro results. This study shows the paradigm-changing potential of NPs to combat the disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

et al. 2021

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“…MicroRNAs (miRs) represent major epigenetic regulators, and their implications as potential diagnostic, prognostic, and therapeutic biological markers in pancreatic cancer have emerged in the last decade [ 46 , 47 , 48 ]. MitomiRs are a subset of microRNAs that tightly control mitochondrial functions.…”

Section: Mitomir and Mitochondria-related Mir Variations In Pdac: Diagnostic Prognostic And Therapeutic Biomarkersmentioning

confidence: 99%

Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers

Moro

2021

IJMS

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Pancreatic cancer is an aggressive disease with poor prognosis. Only about 15–20% of patients diagnosed with pancreatic cancer can undergo surgical resection, while the remaining 80% are diagnosed with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In these cases, chemotherapy and radiotherapy only confer marginal survival benefit. Recent progress has been made in understanding the pathobiology of pancreatic cancer, with a particular effort in discovering new diagnostic and prognostic biomarkers, novel therapeutic targets, and biomarkers that can predict response to chemo- and/or radiotherapy. Mitochondria have become a focus in pancreatic cancer research due to their roles as powerhouses of the cell, important subcellular biosynthetic factories, and crucial determinants of cell survival and response to chemotherapy. Changes in the mitochondrial genome (mtDNA) have been implicated in chemoresistance and metastatic progression in some cancer types. There is also growing evidence that changes in microRNAs that regulate the expression of mtDNA-encoded mitochondrial proteins (mitomiRs) or nuclear-encoded mitochondrial proteins (mitochondria-related miRs) could serve as diagnostic and prognostic cancer biomarkers. This review discusses the current knowledge on the clinical significance of changes of mtDNA, mitomiRs, and mitochondria-related miRs in pancreatic cancer and their potential role as predictors of cancer risk, as diagnostic and prognostic biomarkers, and as molecular targets for personalized cancer therapy.

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“…Therefore, developing new technologies that target both tumour cells and CAFs is essential. Nanoparticles of high-Z materials such as gold nanoparticles (GNPs) have shown promising results as radiosensitizer agents in radiotherapy and as vectors for targeted-drug delivery in chemotherapy [4][5]12]. There is also tremendous evidence that GNPs and low concentrations of anticancer drugs can sensitize cancer cells to radiotherapy in monoculture in vitro environment [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticles Uptake in Monoculture vs Co-culture of Pancreatic Cancer Cells

Abdulaziz¹,

Smazynski²,

Chithrani³

2021

Proceedings of the 7th World Congress on New Technologies

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Despite the advancements in medicine in the last decade, pancreatic cancer is still one of the deadliest types of cancers with a survival rate of less than 7%. The location of pancreas, late detection, the metastatic nature of the disease, and the condensed desmoplasia and stroma of the tumour mass render existing therapeutics inadequate for many patients. Nanotechnology has emerged as a possible solution for hard-to-treat cancers. High atomic number materials such as gold nanoparticles (GNPs) have radiosensitizing properties and could also be used as a drug carrier to precisely deliver drugs to their target. Most recent studies have focused on the radiosensitizing effects of gold in monocultures of cancer cells. However, co-culture systems differ from monoculture systems in the cell-to-cell intercommunication between the different cell lines used. Cancer associated fibroblasts (CAFs) are another very important components of the tumour microenvironment that plays a negative role in radio-and chemo-resistance. They communicate directly with cancer cells to help promote tumour growth. In this paper, separation of cancer cells from CAFs, and GNPs uptake in co-cultures of cancer cells and CAFs vs monocultures were investigated. Successful separation between the two cell lines used was attainable with high accuracy using magnetic beads separation. Our data show that GNP uptakes is roughly the same between cells of the same type whether grown in monoculture or in co-culture. The results also reveal a much higher uptake of GNPs by CAFs compared to tumour cells. We conclude that targeting tumour cells and CAFs in co-culture using radiosensitizing GNPs is feasible and is expected to yield encouraging outcomes.

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The Emerging Role of miRNAs for the Radiation Treatment of Pancreatic Cancer

Cited by 16 publications

References 140 publications

Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

Investigation of Nano-Bio Interactions within a Pancreatic Tumor Microenvironment for the Advancement of Nanomedicine in Cancer Treatment

Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers

Gold Nanoparticles Uptake in Monoculture vs Co-culture of Pancreatic Cancer Cells

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