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Cancer and Immunology

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Cancer and Immunology

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Cancer and Immunology

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Biomedical Science

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Abstract

Background: Pancreatic cancer is the third leading cause of death from cancer and is predicted to affect 67,440 people globally in 2025. Diagnosis of pancreatic cancer is almost synonymous with mortality due to late diagnosis. CA 19-9, the only FDA approved biomarker currently used to diagnose pancreatic cancer, has low sensitivity and specificity at the earlier stage of cancer presentation. Due to the aggressive nature of pancreatic cancer in combination with the lack of identifiable markers, the need to develop new markers specific to pancreatic cancer is highly pertinent. Exosomes are extracellular vehicles that have been utilized by cancer cells to promote tumorigenesis via promotion of immune escape, angiogenesis, cell proliferation, and transfer of drug resistance receptors. Analysis of exosome content has recently increased in popularity in pancreatic cancer diagnosis because of its ability to indicate the extent of the tumor involvement. Its accessibility non-invasively via a liquid biopsy and stability due to a lipid-double membrane covering makes its utilization appealing. This review aims to determine the role of exosomes in the diagnosis and therapy for pancreatic cancer.

Methods: We used PubMed to conduct a literature review of biomarkers as well as therapies utilizing exosomes in pancreatic cancer. We used the keywords “exosomes”, “pancreatic cancer”, “biomarker”, “diagnostic marker”, and “therapy” in various combinations to obtain the incorporated results.

Results: Most studies looking to identify diagnostic markers utilized serum derived exosomes, although those from saliva and pancreatic ductal fluid were also utilized. Several different micro RNAs, long noncoding RNAs, proteins, and lipids contained in exosomes were found to have significance in early pancreatic cancer diagnosis. Several exosome microRNAs even displayed higher sensitivity compared to CA 19-9 levels in diagnosis, highlighting the potential of these markers in early diagnosis. However, it is important to note that most of these studies were conducted in vitro.

The role of exosomes in cancer has also been useful as therapeutic targets via exosome inhibition and its use as transport vehicles. Certain exosomes like those from cancer adjacent fibroblasts have been proven to target specifically pancreatic cancer cells. Inhibition of exosome biogenesis, secretion, or reuptake has been beneficial in slowing pancreatic tumor angiogenesis and metastasis. When loaded into exosomes, drugs like Gemcitabine had increased effectiveness, curcumin had increased bioavailability, and inhibitory genes like small interfering RNA as well as anti-cancer drugs like Ormeloxifene decreased tumor metastasis in pancreatic tumor cells. This is predicted to be partly due to a decrease in immunotherapy resistance otherwise often caused by macrophage phagocytosis.

Conclusion: This review highlights the potential of the usage of exosomes in early diagnosis and therapy of pancreatic cancer. However, improved standardization and efficiency of the exosome isolation and utilization process as well as large-scale clinical trials are still required to implement the use of exosomes clinically.

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Poster

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The Role of Exosomes in Diagnosis and Therapy of Pancreatic Cancer

Background: Pancreatic cancer is the third leading cause of death from cancer and is predicted to affect 67,440 people globally in 2025. Diagnosis of pancreatic cancer is almost synonymous with mortality due to late diagnosis. CA 19-9, the only FDA approved biomarker currently used to diagnose pancreatic cancer, has low sensitivity and specificity at the earlier stage of cancer presentation. Due to the aggressive nature of pancreatic cancer in combination with the lack of identifiable markers, the need to develop new markers specific to pancreatic cancer is highly pertinent. Exosomes are extracellular vehicles that have been utilized by cancer cells to promote tumorigenesis via promotion of immune escape, angiogenesis, cell proliferation, and transfer of drug resistance receptors. Analysis of exosome content has recently increased in popularity in pancreatic cancer diagnosis because of its ability to indicate the extent of the tumor involvement. Its accessibility non-invasively via a liquid biopsy and stability due to a lipid-double membrane covering makes its utilization appealing. This review aims to determine the role of exosomes in the diagnosis and therapy for pancreatic cancer.

Methods: We used PubMed to conduct a literature review of biomarkers as well as therapies utilizing exosomes in pancreatic cancer. We used the keywords “exosomes”, “pancreatic cancer”, “biomarker”, “diagnostic marker”, and “therapy” in various combinations to obtain the incorporated results.

Results: Most studies looking to identify diagnostic markers utilized serum derived exosomes, although those from saliva and pancreatic ductal fluid were also utilized. Several different micro RNAs, long noncoding RNAs, proteins, and lipids contained in exosomes were found to have significance in early pancreatic cancer diagnosis. Several exosome microRNAs even displayed higher sensitivity compared to CA 19-9 levels in diagnosis, highlighting the potential of these markers in early diagnosis. However, it is important to note that most of these studies were conducted in vitro.

The role of exosomes in cancer has also been useful as therapeutic targets via exosome inhibition and its use as transport vehicles. Certain exosomes like those from cancer adjacent fibroblasts have been proven to target specifically pancreatic cancer cells. Inhibition of exosome biogenesis, secretion, or reuptake has been beneficial in slowing pancreatic tumor angiogenesis and metastasis. When loaded into exosomes, drugs like Gemcitabine had increased effectiveness, curcumin had increased bioavailability, and inhibitory genes like small interfering RNA as well as anti-cancer drugs like Ormeloxifene decreased tumor metastasis in pancreatic tumor cells. This is predicted to be partly due to a decrease in immunotherapy resistance otherwise often caused by macrophage phagocytosis.

Conclusion: This review highlights the potential of the usage of exosomes in early diagnosis and therapy of pancreatic cancer. However, improved standardization and efficiency of the exosome isolation and utilization process as well as large-scale clinical trials are still required to implement the use of exosomes clinically.

 

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