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Treatment of Pancreatic Cancer by Aptamer Conjugated C/EBPα-saRNA

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RNA Activation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 983))

Abstract

Pancreatic cancer is estimated to become the second-leading cause of cancer-related mortality by 2020. While the death rates of most other cancers continue to decline recently, the death rates of pancreatic cancer are still increasing, with less than 5% of patients achieving 5-year survival. Despite great efforts to improve treatment with combinational therapies in pancreatic cancer patients, limited progress has been made. V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) has been depicted as a therapeutic target in pancreatic cancer for many years. However, the clinical outcome of KRAS-directed therapies has not been successful, suggesting that KRAS is an undruggable target. For the new druggable target, epigenetically silenced transcriptional factor C/EBPα (CCAAT/enhancer-binding protein α), upregulator of a strong inhibitor of cell proliferation (p21), is upregulated by small activating RNA (saRNA) in pancreatic cancer. For the cell type-specific delivery, pancreatic cancer-specific 2′-Fluoropyrimidine RNA-aptamers (2′F-RNAs) are conjugated with C/EBPα-saRNA via sticky bridge sequences. The conjugates of aptamer–C/EBPα-saRNA upregulate the expression of C/EBPα in vitro and inhibit the tumor growth in vivo. It suggests that aptamer-mediated targeted delivery of therapeutic C/EBPα-saRNA might be the effective therapeutics under the current therapeutic modality failure in pancreatic cancer.

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Acknowledgments

This chapter is based on the published paper “Targeted Delivery of C/EBPα-saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo” in Mol Ther (2016); 24 (6), 1106–1116.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1500 E Duarte Rd, Duarte, CA, USA

    Sorah Yoon & John J. Rossi

  2. Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, 1500 E Duarte Rd, Duarte, CA, USA

    John J. Rossi

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  1. Sorah Yoon
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Correspondence to John J. Rossi .

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Editors and Affiliations

  1. Laboratory of Molecular Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China

    Long-Cheng Li

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Yoon, S., Rossi, J.J. (2017). Treatment of Pancreatic Cancer by Aptamer Conjugated C/EBPα-saRNA. In: Li, LC. (eds) RNA Activation. Advances in Experimental Medicine and Biology, vol 983. Springer, Singapore. https://doi.org/10.1007/978-981-10-4310-9_12

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