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Review
. 2021 Oct 21;27(39):6527-6550.
doi: 10.3748/wjg.v27.i39.6527.

Therapeutic resistance in pancreatic ductal adenocarcinoma: Current challenges and future opportunities

Aditi Jain  1 , Vikas Bhardwaj  2
Affiliations
Review

Therapeutic resistance in pancreatic ductal adenocarcinoma: Current challenges and future opportunities

Aditi Jain et al. World J Gastroenterol. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Although chemotherapeutic regimens such as gemcitabine+ nab-paclitaxel and FOLFIRINOX (FOLinic acid, 5-Fluroruracil, IRINotecan, and Oxaliplatin) significantly improve patient survival, the prevalence of therapy resistance remains a major roadblock in the success of these agents. This review discusses the molecular mechanisms that play a crucial role in PDAC therapy resistance and how a better understanding of these mechanisms has shaped clinical trials for pancreatic cancer chemotherapy. Specifically, we have discussed the metabolic alterations and DNA repair mechanisms observed in PDAC and current approaches in targeting these mechanisms. Our discussion also includes the lessons learned following the failure of immunotherapy in PDAC and current approaches underway to improve tumor's immunological response.

Keywords: DNA repair; Immunotherapy; Metabolism; Pancreatic cancer; Therapy-resistance.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflict of interests for this article.

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