Exploring the potential of asparagine restriction in solid cancer treatment: recent discoveries, therapeutic implications, and challenges

Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022. https://doi.org/10.1158/2159-8290.CD-21-1059.

Article  PubMed  Google Scholar 

Navarro C, Ortega Á, Santeliz R, Garrido B, Chacín M, Galban N, et al. Metabolic reprogramming in cancer cells: emerging molecular mechanisms and novel therapeutic approaches. Pharmaceutics. 2022. https://doi.org/10.3390/pharmaceutics14061303.

Article  PubMed  PubMed Central  Google Scholar 

Vettore L, Westbrook RL, Tennant DA. New aspects of amino acid metabolism in cancer. Br J Cancer. 2020. https://doi.org/10.1038/s41416-019-0620-5.

Article  PubMed  Google Scholar 

Knott SRV, Wagenblast E, Khan S, Kim SY, Soto M, Wagner M, et al. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature. 2018;554:378–81.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pavlova NN, Hui S, Ghergurovich JM, Fan J, Intlekofer AM, White RM, et al. As extracellular glutamine levels decline, asparagine becomes an essential amino acid. Cell Metab. 2018;27:428-438.e5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lefin N, Miranda J, Beltrán JF, Belén LH, Effer B, Pessoa A, et al. Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems. Front Pharmacol. 2023.

Sun J, Nagel R, Zaal EA, Ugalde AP, Han R, Proost N, et al. SLC 1A3 contributes to L-asparaginase resistance in solid tumors. EMBO J. 2019. https://doi.org/10.15252/embj.2019102147.

Article  PubMed  PubMed Central  Google Scholar 

Nakamura A, Nambu T, Ebara S, Hasegawa Y, Toyoshima K, Tsuchiya Y, et al. Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response. Proc Natl Acad Sci USA. 2018. https://doi.org/10.1073/pnas.1805523115.

Article  PubMed  PubMed Central  Google Scholar 

Pathria G, Lee JS, Hasnis E, Tandoc K, Scott DA, Verma S, et al. Translational reprogramming marks adaptation to asparagine restriction in cancer. Nat Cell Biol. 2019;21:1590.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Recouvreux MV, Grenier SF, Zhang Y, Esparza E, Lambies G, Galapate CM, et al. Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma. Nat Cancer. 2023. https://doi.org/10.1038/s43018-023-00649-1.

Article  PubMed  PubMed Central  Google Scholar 

Karpel-Massler G, Ramani D, Shu C, Halatsch ME, Westhoff MA, Bruce JN, et al. Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo. Oncotarget. 2016;7:33512.

Article  PubMed  PubMed Central  Google Scholar 

Chandel NS. Amino acid metabolism. Cold Spring Harb Perspect Biol. 2021;13:a040584.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kandasamy P, Zlobec I, Nydegger DT, Pujol-Giménez J, Bhardwaj R, Shirasawa S, et al. Oncogenic KRAS mutations enhance amino acid uptake by colorectal cancer cells via the hippo signaling effector YAP1. Mol Oncol. 2021;15:2782.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taurino G, Chiu M, Bianchi MG, Griffini E, Bussolati O. The SLC38A5 /SNAT5 amino acid transporter: from pathophysiology to pro-cancer roles in the tumor microenvironment. Am J Physiol Cell Physiol. 2023;325:C550.

Article  CAS  PubMed  Google Scholar 

Magi S, Piccirillo S, Amoroso S, Lariccia V. Excitatory amino acid transporters (Eaats): glutamate transport and beyond. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20225674.

Article  PubMed  PubMed Central  Google Scholar 

Krall AS, Xu S, Graeber TG, Braas D, Christofk HR. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun. 2016. https://doi.org/10.1038/ncomms11457.

Article  PubMed  PubMed Central  Google Scholar 

Luo M, Brooks M, Wicha MS. Asparagine and glutamine: co-conspirators fueling metastasis. Cell Metab. 2018;27:947–9. https://doi.org/10.1016/j.cmet.2018.04.012.

Article  CAS  PubMed  Google Scholar 

Zhang J, Fan J, Venneti S, Cross JR, Takagi T, Bhinder B, et al. Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell. 2014;56:205.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cui H, Darmanin S, Natsuisaka M, Kondo T, Asaka M, Shindoh M, et al. Enhanced expression of asparagine synthetase under glucose-deprived conditions protects pancreatic cancer cells from apoptosis induced by glucose deprivation and cisplatin. Cancer Res. 2007;67:3345.

Article  CAS  PubMed  Google Scholar 

Yang H, He X, Zheng Y, Feng W, Xia X, Yu X, et al. Down-regulation of asparagine synthetase induces cell cycle arrest and inhibits cell proliferation of breast cancer. Chem Biol Drug Des. 2014;84:578.

Article  CAS  PubMed  Google Scholar 

Xu Y, Lv F, Zhu X, Wu Y, Shen X. Loss of asparagine synthetase suppresses the growth of human lung cancer cells by arresting cell cycle at G0/G1 phase. Cancer Gene Ther. 2016;23:287.

Article  CAS  PubMed  Google Scholar 

Yu Q, Wang X, Wang L, Zheng J, Wang J, Wang B. Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells. Scand J Gastroenterol. 2016;51:1220.

Article  CAS  PubMed  Google Scholar 

Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021. https://doi.org/10.1038/s41392-021-00780-4.

Article  PubMed  PubMed Central  Google Scholar 

Kerk SA, Papagiannakopoulos T, Shah YM, Lyssiotis CA. Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment. Nat Rev Cancer. 2021. https://doi.org/10.1038/s41568-021-00375-9.

Article  PubMed  PubMed Central  Google Scholar 

Suzuki T, Kishikawa T, Sato T, Takeda N, Sugiura Y, Seimiya T, et al. Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells. Cancer Gene Ther. 2022;29:505.

Article  CAS  PubMed  Google Scholar 

Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 1979;2009:325.

Google Scholar 

Chidley C, Darnell AM, Gaudio BL, Lien EC, Barbeau AM, Vander Heiden MG, et al. A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments. Nat Cell Biol. 2024;26:825–38. https://doi.org/10.1038/s41556-024-01402-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Toda K, Kawada K, Iwamoto M, Inamoto S, Sasazuki T, Shirasawa S, et al. Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia. 2016;18:654.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gwinn DM, Lee AG, Briones-Martin-del-Campo M, Conn CS, Simpson DR, Scott AI, et al. Oncogenic KRAS regulates amino acid homeostasis and asparagine biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase. Cancer Cell. 2018;33:91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang R, Li X, Wu Y, Zhang G, Liu X, Li

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