Department of Medical Education, College of Medicine, University of Central Florida, Orlando, FL.
Int J Cancer. 2018 May 15;142(10):1968-1976. doi: 10.1002/ijc.31155. Epub 2017 Dec 13.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest major cancers, with a five year survival rate of less than 8%. With current therapies only giving rise to modest life extension, new approaches are desperately needed. Even though targeting polyamine metabolism is a proven anticancer strategy, there are no reports, which thoroughly survey the literature describing the role of polyamine biosynthesis and transport in PDAC. This review seeks to fill this void by describing what is currently known about polyamine metabolism in PDAC and identifies new targets and opportunities to treat this disease. Due to the pleiotropic effects that polyamines play in cells, this review covers diverse areas ranging from polyamine metabolism (biosynthesis, catabolism and transport), as well as the potential role of polyamines in desmoplasia, autophagy and immune privilege. Understanding these diverse roles provides the opportunity to design new therapies to treat this deadly cancer via polyamine depletion.
胰腺导管腺癌(PDAC)是最致命的主要癌症之一,五年生存率不足 8%。由于目前的治疗方法只能适度延长生命,因此迫切需要新的方法。尽管靶向多胺代谢是一种经过验证的抗癌策略,但目前尚无全面综述文献中描述多胺生物合成和转运在 PDAC 中作用的报道。本文旨在通过描述 PDAC 中多胺代谢的现有知识,并确定治疗这种疾病的新靶点和机会,来填补这一空白。由于多胺在细胞中发挥的多效性作用,本综述涵盖了从多胺代谢(生物合成、分解代谢和转运)到多胺在纤维增生、自噬和免疫豁免中的潜在作用等多个领域。了解这些不同的作用为通过多胺耗竭设计治疗这种致命癌症的新疗法提供了机会。