Document Type
Article
Publication Date
12-12-2018
Abstract
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity. However, alternative metabolic targets beyond DNA may prove to be much more effective. PDA cells are forced to live within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. Thus, PDA cells must possess biochemical flexibility in order to adapt to austere conditions. A better understanding of the metabolic dependencies required by PDA to survive and thrive within a harsh metabolic milieu could reveal specific metabolic vulnerabilities. These molecular requirements can then be targeted therapeutically, and would likely be associated with a clinically significant therapeutic window since the normal tissue is so well-perfused with an abundant nutrient supply. Recent work has uncovered a number of promising therapeutic targets in the metabolic domain, and clinicians are already translating some of these discoveries to the clinic. In this review, we highlight mitochondria metabolism, non-canonical nutrient acquisition pathways (macropinocytosis and use of pancreatic stellate cell-derived alanine), and redox homeostasis as compelling therapeutic opportunities in the metabolic domain.
Recommended Citation
Vaziri-Gohar, Ali; Zarei, Mahsa; Brody, Jonathan R.; and Winter, Jordan M., "Metabolic Dependencies in Pancreatic Cancer." (2018). Department of Surgery Faculty Papers. Paper 169.
https://jdc.jefferson.edu/surgeryfp/169
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
30631752
Language
English
Comments
This article has been peer reviewed. It is the author’s final published version in Frontiers in Oncology, Volume 8, Issue DEC, December 2018, Article number 617.
The published version is available at https://doi.org/10.3389/fonc.2018.00617. Copyright © Vaziri-Gohar
First published by Frontiers Media.
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A Corrigendum on Metabolic Dependencies in Pancreatic Cancer by Vaziri-Gohar, A., Zarei, M., Brody, J. R., and Winter, J. M. (2018). Front. Oncol. 8:617. doi: 10.3389/fonc.2018.00617 In the original article, all references for in Tables 1, 2 were incorrectly listed. The corrected references for both Table 1 and Table 2 have been corrected and provided below. (Table Presented) In the original article, references in Table 2 were not provided in the reference list. The references have now been inserted. The authors apologize for these errors and state that they do not change the scientific conclusions of the article in any way. The original article has been updated.