Impact of posttranslational modifications in pancreatic carcinogenesis and treatments.

Abstract

Pancreatic cancer (PC) is a highly aggressive cancer, with a 9% 5-year survival rate and a high risk of recurrence. In part, this is because PC is composed of heterogeneous subgroups with different biological and functional characteristics and personalized anticancer treatments are required. Posttranslational modifications (PTMs) play an important role in modifying protein functions/roles and are required for the maintenance of cell viability and biological processes; thus, their dysregulation can lead to disease. Different types of PTMs increase the functional diversity of the proteome, which subsequently influences most aspects of normal cell biology or pathogenesis. This review primarily focuses on ubiquitination, SUMOylation, and NEDDylation, as well as the current understanding of their roles and molecular mechanisms in pancreatic carcinogenesis. Additionally, we briefly summarize studies and clinical trials on PC treatments to advance our knowledge of drugs available to target the ubiquitination, SUMOylation, and NEDDylation PTM types. Further investigation of PTMs could be a critical field of study in relation to PC, as they have been implicated in the initiation and progression of many other types of cancer.