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Proteostasis Dysregulation in Pancreatic Cancer

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Proteostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1233))

Abstract

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin–proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitin-ligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.

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Acknowledgments

We apologize to all the authors, whose original work could not be cited due to space limitations. This work was supported by grant to C.I.H. from the Academy of Finland (#297776), Sigrid Jusélius Foundation and Medicinska Understödsföreningen Liv och Hälsa r.f. The authors would like to acknowledge networking support by the Proteostasis COST Action (BM1307).

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Authors and Affiliations

  1. Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland

    Leena Arpalahti & Carina I. Holmberg

  2. Research Programs Unit, Translational Cancer Medicine Program, University of Helsinki, Helsinki, Finland

    Caj Haglund

  3. Department of Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

    Caj Haglund

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  1. Leena Arpalahti
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  2. Caj Haglund
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  3. Carina I. Holmberg
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Correspondence to Carina I. Holmberg .

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  1. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    Rosa Barrio

  2. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    James D. Sutherland

  3. Centre Pierre Potier, ITAV, Toulouse Cedex 1, France

    Manuel S. Rodriguez

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Arpalahti, L., Haglund, C., Holmberg, C.I. (2020). Proteostasis Dysregulation in Pancreatic Cancer. In: Barrio, R., Sutherland, J., Rodriguez, M. (eds) Proteostasis and Disease . Advances in Experimental Medicine and Biology, vol 1233. Springer, Cham. https://doi.org/10.1007/978-3-030-38266-7_4

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