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Review
. 2023 Jan 9:13:1108776.
doi: 10.3389/fphar.2022.1108776. eCollection 2022.

The role of metabolic reprogramming in pancreatic cancer chemoresistance

Chang Liu  1 , Changfeng Li  1 , Yuanda Liu  1
Affiliations
Review

The role of metabolic reprogramming in pancreatic cancer chemoresistance

Chang Liu et al. Front Pharmacol. .

Abstract

Pancreatic cancer is characterized by hidden onset, high malignancy, and early metastasis. Although a few cases meet the surgical indications, chemotherapy remains the primary treatment, and the resulting chemoresistance has become an urgent clinical problem that needs to be solved. In recent years, the importance of metabolic reprogramming as one of the hallmarks of cancers in tumorigenesis has been validated. Metabolic reprogramming involves glucose, lipid, and amino acid metabolism and interacts with oncogenes to affect the expression of key enzymes and signaling pathways, modifying the tumor microenvironment and contributing to the occurrence of drug tolerance. Meanwhile, the mitochondria are hubs of the three major nutrients and energy metabolisms, which are also involved in the development of drug resistance. In this review, we summarized the characteristic changes in metabolism during the progression of pancreatic cancer and their impact on chemoresistance, outlined the role of the mitochondria, and summarized current studies on metabolic inhibitors.

Keywords: chemoresistance; fatty acid synthesis; glutamine metabolism; glycolysis; metabolic reprogramming; pancreatic cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Metabolic reprogramming in pancreatic cancer. Red arrowheads represent the effects induced by mutant KRAS: upward means upregulation; downward means downregulation. The black symbols represent the changes induced by other reasons (e.g., HIF-1α、c-MYC). Abbreviations: GLUT, glucose transporter; HK, hexokinase; PFK, phosphofructokinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ENO, enolase; PK, pyruvate kinase; LDH, lactate dehydrogenase; MCT, monocarboxylic acid transporters; PDH, pyruvate dehydrogenase; α-KG, α-ketoglutarate; ASCT2/SLC1A5, alanine/serine/cysteine transporter 2/SLC1A5; GSH, glutathione; GLS, glutaminase; GDH, glutamate dehydrogenase; IDH2, isocitrate dehydrogenase 2; GOT1, aspartate transaminase 1; GOT2, aspartate transaminase 2; GPT, alanine transaminase; α-KGDH, α-KG dehydrogenase; ME, malic enzyme; MDH1, malate dehydrogenase 1; ACLY, ATP-citrate lyase; ACC, acetyl CoA carboxylase; FASN, fatty acid synthase.
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References

    1. Aguilera K. Y., Le T., Riahi R., Lay A. R., Hinz S., Saadat E. A., et al. (2022). Porcupine inhibition disrupts mitochondrial function and homeostasis in WNT ligand-addicted pancreatic cancer. Mol. Cancer Ther. 21 (6), 936–947. 10.1158/1535-7163.Mct-21-0623 - DOI - PMC - PubMed
    1. Alistar A., Morris B. B., Desnoyer R., Klepin H. D., Hosseinzadeh K., Clark C., et al. (2017). Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: A single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol. 18 (6), 770–778. 10.1016/s1470-2045(17)30314-5 - DOI - PMC - PubMed
    1. Alo P. L., Amini M., Piro F., Pizzuti L., Sebastiani V., Botti C., et al. (2007). Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma. Anticancer Res. 27 (4), 2523–2527. - PubMed
    1. Anderson N. M., Mucka P., Kern J. G., Feng H. (2018). The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell 9 (2), 216–237. 10.1007/s13238-017-0451-1 - DOI - PMC - PubMed
    1. Bandara I. A., Baltatzis M., Sanyal S., Siriwardena A. K. (2018). Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer. World J. Surg. Oncol. 16 (1), 56. 10.1186/s12957-018-1360-3 - DOI - PMC - PubMed

Grants and funding

This review was supported by grants from the Natural Science Foundation of China (Nos. 81872323 and 82073299), Finance Department of Jilin Province (2021SCZ12) and project of China-Japan Union Hospital of Jilin University (KYXZ2022JC06).

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