• 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • 2021-03
  • br Funding br Not applicable


    Not applicable.
    We thank the editor, Dr. Shashikant Kulkarni, and anonymous reviewers for their helpful suggestions which improved the manuscript. We are grateful to our colleagues at the National Cancer Institute, Drs. Joanna Shih, Jianwen Fang, William Reinhold, Beverly Teicher, Toby Hecht, Yingdong Zhao, and Lisa McShane for helpful and productive discussions about cell line resources, drug sensitivity values, and statistical and bioinformatic questions related to this manuscript.
    The views expressed in this article are the personal opin-ions of the authors and do not necessarily reflect policy of the US National Cancer Institute.
    Conflict of interest
    The authors declare no competing interests with this research.
    Supplementary materials
    [2] Rosenzweig A, Blenis J, Gomes AP. Beyond the Warburg Ef-fect: how do cancer MG132 regulate one-carbon metabolism? Front Cell Dev Biol 2018;6:90.
    [4] Stover PJ. Polymorphisms in 1-carbon metabolism, epigenet-ics and folate-related pathologies. J Nutrigenet Nutrigenomics 2011;4:293–305.
    [5] Gustafsson Sheppard N, Jarl L, Mahadessian D, Strittmat-ter L, Schmidt A, Madhusudan N, Tegner J, Lundberg EK, Asplund A, Jain M, Nilsson R. The folate-coupled enzyme MTHFD2 is a nuclear protein and promotes cell proliferation. Sci Rep 2015;5:15029.
    [11] Kim YI. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 2005;135:2703–9.
    [12] Vazquez A, Tedeschi PM, Bertino JR. Overexpression of the mitochondrial folate and glycine-serine pathway: a new de-terminant of methotrexate selectivity in tumors. Cancer Res 2013;73:478–82.
    [13] Branda RF, Nigels E, Lafayette AR, Hacker M. Nutritional folate status influences the efficacy and toxicity of chemotherapy in rats. Blood 1998;92:2471–6.
    [14] Hazra A, Wu K, Kraft P, Fuchs CS, Giovannucci EL, Hunter DJ. Twenty-four non-synonymous polymorphisms in the one-car-bon metabolic pathway and risk of colorectal adenoma in the Nurses’ Health Study. Carcinogenesis 2007;28:1510–19.
    [16] Novakovic P, Stempak JM, Sohn KJ, Kim YI. Effects of fo-late deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis 2006;27:916–24.
    [21] Krushkal J, Zhao Y, Hose C, Monks A, Doroshow JH, Simon R. Concerted changes in transcriptional regulation of genes in-volved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment. Clin Epigenetics 2016;8:73.
    [22] CCLE Cancer Cell Line Encyclopedia. Available at: http://www. Accessed 6 August 2018.
    [23] CCLE Cancer Cell Line Encyclopedia legacy portal. Avail-able at: searchResult Accessed 6 August 2018.
    [24] CellminerCDB. Available at: cellminercdb/ Accessed 22 August 2018.
    [25] Genomics of Drug Sensitivity in Cancer data download site. Available at: Ac-cessed June 12, 2018.
    [26] Barretina J, Caponigro G, Stransky N, Venkatesan K, Mar-golin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jane-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu GK, Yu J, Aspesi P Jr, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, Sougnez C, Onofrio RC, Liefeld T, MacConaill L, Winckler W, Reich M, Li N, Mesirov JP, Gabriel SB, Getz G, Ardlie K, Chan V, Myer VE, Weber BL, Porter J, Warmuth M, Finan P, Harris JL, Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, Garraway LA. The Cancer Cell Line Encyclope-dia enables predictive modelling of anticancer drug sensitivity. Nature 2012;483:603–7.
    [27] Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP, Schubert M, Aben N, Goncalves E, Barthorpe S, Lightfoot H, Cokelaer T, Greninger P, van Dyk E, Chang H, de Silva H, Heyn H, Deng X, Egan RK, Liu Q, Mironenko T, Mitropou-los X, Richardson L, Wang J, Zhang T, Moran S, Sayols S, Soleimani M, Tamborero D, Lopez-Bigas N, Ross-Macdon-ald P, Esteller M, Gray NS, Haber DA, Stratton MR, Benes CH, Wessels LF, Saez-Rodriguez J, McDermott U, Garnett MJ. A landscape of pharmacogenomic interactions in cancer. Cell 2016;166:740–54.
    [28] Shuvalov O, Petukhov A, Daks A, Fedorova O, Vasileva E, Barlev NA. One-carbon metabolism and nucleotide biosyn-thesis as attractive targets for anticancer therapy. Oncotarget 2017;8:23955–77.