Novel Insights on Lipid Metabolism Alterations in Drug Resistance in Cancer

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Jun 1

PMID 35646898

Authors

Ruixue Yang

Mei Yi

Bo Xiang

Affiliations

Soon will be listed here.

Abstract

Chemotherapy is one of the primary treatments for most human cancers. Despite great progress in cancer therapeutics, chemotherapy continues to be important for improving the survival of cancer patients, especially for those who has unresectable metastatic tumors or fail to respond to immunotherapy. However, intrinsic or acquired chemoresistance results in tumor recurrence, which remains a major obstacle in anti-cancer treatment. The high prevalence of chemoresistant cancer makes it urgent to deepen our understanding on chemoresistance mechanisms and to develop novel therapeutic strategies. Multiple mechanisms, including drug efflux, enhanced DNA damage reparability, increased detoxifying enzymes levels, presence of cancer stem cells (CSCs), epithelial mesenchymal transition (EMT), autophagy, ferroptosis and resistance to apoptosis, underlie the development of chemoresistance. Recently, accumulating evidence suggests that lipid metabolism alteration is closely related to drug resistance in tumor. Targeting lipid metabolism in combination with traditional chemotherapeutic drugs is a promising strategy to overcome drug resistance. Therefore, this review compiles the current knowledge about aberrant lipid metabolism in chemoresistant cancer, mainly focusing on aberrant fatty acid metabolism, and presents novel therapeutic strategies targeting altered lipid metabolism to overcome chemoresistance in cancer.

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References

Pisanu M, Noto A, De Vitis C, Morrone S, Scognamiglio G, Botti G . Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett. 2017; 406:93-104. DOI: 10.1016/j.canlet.2017.07.027. View

Liu Q, Luo Q, Halim A, Song G . Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer. Cancer Lett. 2017; 401:39-45. DOI: 10.1016/j.canlet.2017.05.002. View

Zhang J, Song F, Zhao X, Jiang H, Wu X, Wang B . EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer. Mol Cancer. 2017; 16(1):127. PMC: 5518108. DOI: 10.1186/s12943-017-0704-x. View

Hultsch S, Kankainen M, Paavolainen L, Kovanen R, Ikonen E, Kangaspeska S . Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer. 2018; 18(1):850. PMC: 6109356. DOI: 10.1186/s12885-018-4757-z. View

Talebi A, Dehairs J, Rambow F, Rogiers A, Nittner D, Derua R . Sustained SREBP-1-dependent lipogenesis as a key mediator of resistance to BRAF-targeted therapy. Nat Commun. 2018; 9(1):2500. PMC: 6021375. DOI: 10.1038/s41467-018-04664-0. View

Porstmann T, Griffiths B, Chung Y, Delpuech O, Griffiths J, Downward J . PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene. 2005; 24(43):6465-81. DOI: 10.1038/sj.onc.1208802. View

Eckford P, Sharom F . ABC efflux pump-based resistance to chemotherapy drugs. Chem Rev. 2009; 109(7):2989-3011. DOI: 10.1021/cr9000226. View

Lee J, Kim W, Bae K, Lee S, Lee E . Lipid Metabolism and Ferroptosis. Biology (Basel). 2021; 10(3). PMC: 8000263. DOI: 10.3390/biology10030184. View

Govaere O, Wouters J, Petz M, Vandewynckel Y, Van den Eynde K, Van Den Broeck A . Laminin-332 sustains chemoresistance and quiescence as part of the human hepatic cancer stem cell niche. J Hepatol. 2015; 64(3):609-17. DOI: 10.1016/j.jhep.2015.11.011. View

10.

Igal R . Stearoyl CoA desaturase-1: New insights into a central regulator of cancer metabolism. Biochim Biophys Acta. 2016; 1861(12 Pt A):1865-1880. DOI: 10.1016/j.bbalip.2016.09.009. View

11.

Liu H, Wu X, Dong Z, Luo Z, Zhao Z, Xu Y . Fatty acid synthase causes drug resistance by inhibiting TNF-α and ceramide production. J Lipid Res. 2013; 54(3):776-785. PMC: 3617951. DOI: 10.1194/jlr.M033811. View

12.

Tung S, Shi Y, Wong K, Zhu F, Gorczynski R, Laister R . PPARα and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia. Blood. 2013; 122(6):969-80. DOI: 10.1182/blood-2013-03-489468. View

13.

Farese Jr R, Walther T . Lipid droplets finally get a little R-E-S-P-E-C-T. Cell. 2009; 139(5):855-60. PMC: 3097139. DOI: 10.1016/j.cell.2009.11.005. View

14.

Souchek J, Davis A, Hill T, Holmes M, Qi B, Singh P . Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells. Mol Cancer Ther. 2017; 16(9):1819-1830. PMC: 5598554. DOI: 10.1158/1535-7163.MCT-17-0013. View

15.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

16.

Steinberg G, Carling D . AMP-activated protein kinase: the current landscape for drug development. Nat Rev Drug Discov. 2019; 18(7):527-551. DOI: 10.1038/s41573-019-0019-2. View

17.

Shah S, Carriveau W, Li J, Campbell S, Kopinski P, Lim H . Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism. Oncotarget. 2016; 7(28):43713-43730. PMC: 5190055. DOI: 10.18632/oncotarget.9666. View

18.

Zhao J . Cancer stem cells and chemoresistance: The smartest survives the raid. Pharmacol Ther. 2016; 160:145-58. PMC: 4808328. DOI: 10.1016/j.pharmthera.2016.02.008. View

19.

Huang Y, Bell L, Okamura J, Kim M, Mohney R, Guerrero-Preston R . Phospho-ΔNp63α/SREBF1 protein interactions: bridging cell metabolism and cisplatin chemoresistance. Cell Cycle. 2012; 11(20):3810-27. PMC: 3495824. DOI: 10.4161/cc.22022. View

20.

Hatzivassiliou G, Zhao F, Bauer D, Andreadis C, Shaw A, Dhanak D . ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005; 8(4):311-21. DOI: 10.1016/j.ccr.2005.09.008. View