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Oncogene-Driven Metabolic Alterations in Cancer

  • Min, Hye-Young (Creative Research Initiative Center for concurrent control of emphysema and lung cancer, College of Pharmacy, Seoul National University) ;
  • Lee, Ho-Young (Creative Research Initiative Center for concurrent control of emphysema and lung cancer, College of Pharmacy, Seoul National University)
  • Received : 2017.10.18
  • Accepted : 2017.10.27
  • Published : 2018.01.01

Abstract

Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as KRAS. Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.

Keywords

References

  1. Acquaviva, J., Smith, D. L., Sang, J., Friedland, J. C., He, S., Sequeira, M., Zhang, C., Wada, Y. and Proia, D. A. (2012) Targeting KRASmutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib. Mol. Cancer Ther. 11, 2633-2643. https://doi.org/10.1158/1535-7163.MCT-12-0615
  2. Agrawal, N. R., Bukowski, R. M., Rybicki, L. A., Kurtzberg, J., Cohen, L. J. and Hussein, M. A. (2003) A phase I-II trial of polyethylene glycol-conjugated L-asparaginase in patients with multiple myeloma. Cancer 98, 94-99. https://doi.org/10.1002/cncr.11480
  3. Al-Saffar, N. M., Troy, H., Ramirez de Molina, A., Jackson, L. E., Madhu, B., Griffiths, J. R., Leach, M. O., Workman, P., Lacal, J. C., Judson, I. R. and Chung, Y. L. (2006) Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models. Cancer Res. 66, 427-434. https://doi.org/10.1158/0008-5472.CAN-05-1338
  4. Bar-Peled, L. and Sabatini, D. M. (2014) Regulation of mTORC1 by amino acids. Trends Cell Biol. 24, 400-406. https://doi.org/10.1016/j.tcb.2014.03.003
  5. Baracca, A., Chiaradonna, F., Sgarbi, G., Solaini, G., Alberghina, L. and Lenaz, G. (2010) Mitochondrial Complex I decrease is responsible for bioenergetic dysfunction in K-ras transformed cells. Biochim. Biophys. Acta 1797, 314-323. https://doi.org/10.1016/j.bbabio.2009.11.006
  6. Beckers, A., Organe, S., Timmermans, L., Scheys, K., Peeters, A., Brusselmans, K., Verhoeven, G. and Swinnen, J. V. (2007) Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res. 67, 8180-8187. https://doi.org/10.1158/0008-5472.CAN-07-0389
  7. Benjamin, D., Colombi, M., Moroni, C. and Hall, M. N. (2011) Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 10, 868-880. https://doi.org/10.1038/nrd3531
  8. Bensaad, K. and Harris, A. L. (2013) Cancer metabolism as a therapeutic target: metabolic synthetic lethality. Oncology (Williston Park, N.Y.) 27, 467, 473-474.
  9. Brunelli, L., Caiola, E., Marabese, M., Broggini, M. and Pastorelli, R. (2014) Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells. Oncotarget 5, 4722-4731.
  10. Brunelli, L., Caiola, E., Marabese, M., Broggini, M. and Pastorelli, R. (2016) Comparative metabolomics profiling of isogenic KRAS wild type and mutant NSCLC cells in vitro and in vivo. Sci. Rep. 6, 28398. https://doi.org/10.1038/srep28398
  11. Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543-550. https://doi.org/10.1038/nature13385
  12. Carracedo, A., Cantley, L. C. and Pandolfi, P. P. (2013) Cancer metabolism: fatty acid oxidation in the limelight. Nat. Rev. Cancer 13, 227-232. https://doi.org/10.1038/nrc3483
  13. Carretero, J., Medina, P. P., Blanco, R., Smit, L., Tang, M., Roncador, G., Maestre, L., Conde, E., Lopez-Rios, F., Clevers, H. C. and Sanchez-Cespedes, M. (2007) Dysfunctional AMPK activity, signalling through mTOR and survival in response to energetic stress in LKB1-deficient lung cancer. Oncogene 26, 1616-1625. https://doi.org/10.1038/sj.onc.1209951
  14. Chaudhri, V. K., Salzler, G. G., Dick, S. A., Buckman, M. S., Sordella, R., Karoly, E. D., Mohney, R., Stiles, B. M., Elemento, O., Altorki, N. K. and McGraw, T. E. (2013) Metabolic alterations in lung cancerassociated fibroblasts correlated with increased glycolytic metabolism of the tumor. Mol. Cancer Res. 11, 579-592. https://doi.org/10.1158/1541-7786.MCR-12-0437-T
  15. Chen, P.-H., Cai, L., Kim, H. S., Britt, R., Xiao, G., White, M. A., Minna, J. D. and DeBerardinis, R. J. (2014) Metabolic diversity in human non-small cell lung cancer. Cancer Metab. 2, P13. https://doi.org/10.1186/2049-3002-2-S1-P13
  16. Chiaradonna, F., Sacco, E., Manzoni, R., Giorgio, M., Vanoni, M. and Alberghina, L. (2006) Ras-dependent carbon metabolism and transformation in mouse fibroblasts. Oncogene 25, 5391-5404. https://doi.org/10.1038/sj.onc.1209528
  17. Choi, H., Paeng, J. C., Kim, D. W., Lee, J. K., Park, C. M., Kang, K. W., Chung, J. K. and Lee, D. S. (2013) Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT. Lung Cancer 79, 242-247. https://doi.org/10.1016/j.lungcan.2012.11.021
  18. Clinical Lung Cancer Genome Project (CLCGP) and Network Genomic Medicine (NGM) (2013) A genomics-based classification of human lung tumors. Sci. Transl. Med. 5, 209ra153.
  19. Cloughesy, T. F., Yoshimoto, K., Nghiemphu, P., Brown, K., Dang, J., Zhu, S., Hsueh, T., Chen, Y., Wang, W., Youngkin, D., Liau, L., Martin, N., Becker, D., Bergsneider, M., Lai, A., Green, R., Oglesby, T., Koleto, M., Trent, J., Horvath, S., Mischel, P. S., Mellinghoff, I. K. and Sawyers, C. L. (2008) Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 5, e8. https://doi.org/10.1371/journal.pmed.0050008
  20. Cox, A. D. and Der, C. J. (2010) Ras history: The saga continues. Small GTPases 1, 2-27. https://doi.org/10.4161/sgtp.1.1.12178
  21. Dang, L., Jin, S. and Su, S. M. (2010) IDH mutations in glioma and acute myeloid leukemia. Trends Mol. Med. 16, 387-397. https://doi.org/10.1016/j.molmed.2010.07.002
  22. Davidson, S. M., Papagiannakopoulos, T., Olenchock, B. A., Heyman, J. E., Keibler, M. A., Luengo, A., Bauer, M. R., Jha, A. K., O'Brien, J. P., Pierce, K. A., Gui, D. Y., Sullivan, L. B., Wasylenko, T. M., Subbaraj, L., Chin, C. R., Stephanopolous, G., Mott, B. T., Jacks, T., Clish, C. B. and Vander Heiden, M. G. (2016) Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer. Cell Metab. 23, 517-528. https://doi.org/10.1016/j.cmet.2016.01.007
  23. Dearden, S., Stevens, J., Wu, Y. L. and Blowers, D. (2013) Mutation incidence and coincidence in non small-cell lung cancer: metaanalyses by ethnicity and histology (mutMap). Ann. Oncol. 24, 2371-2376.
  24. Dong, G., Mao, Q., Xia, W., Xu, Y., Wang, J., Xu, L. and Jiang, F. (2016) PKM2 and cancer: the function of PKM2 beyond glycolysis. Oncol. Lett. 11, 1980-1986. https://doi.org/10.3892/ol.2016.4168
  25. Edmunds, L. R., Sharma, L., Kang, A., Lu, J., Vockley, J., Basu, S., Uppala, R., Goetzman, E. S., Beck, M. E., Scott, D. and Prochownik, E. V. (2014) c-Myc programs fatty acid metabolism and dictates acetyl-CoA abundance and fate. J. Biol. Chem. 289, 25382-25392. https://doi.org/10.1074/jbc.M114.580662
  26. Eng, C. P., Sehgal, S. N. and Vezina, C. (1984) Activity of rapamycin (AY-22,989) against transplanted tumors. J. Antibiot. 37, 1231-1237. https://doi.org/10.7164/antibiotics.37.1231
  27. Fan, T. W., Lane, A. N., Higashi, R. M., Farag, M. A., Gao, H., Bousamra, M. and Miller, D. M. (2009) Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM). Mol. Cancer 8, 41. https://doi.org/10.1186/1476-4598-8-41
  28. Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., Li, H., Huet, G., Yuan, Q., Wigal, T., Butt, Y., Ni, M., Torrealba, J., Oliver, D., Lenkinski, R. E., Malloy, C. R., Wachsmann, J. W., Young, J. D., Kernstine, K. and DeBerardinis, R. J. (2017) Lactate Metabolism in Human Lung Tumors. Cell 171, 358-371.e9. https://doi.org/10.1016/j.cell.2017.09.019
  29. Fischer, K., Hoffmann, P., Voelkl, S., Meidenbauer, N., Ammer, J., Edinger, M., Gottfried, E., Schwarz, S., Rothe, G., Hoves, S., Renner, K., Timischl, B., Mackensen, A., Kunz-Schughart, L., Andreesen, R., Krause, S. W. and Kreutz, M. (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109, 3812-3819. https://doi.org/10.1182/blood-2006-07-035972
  30. Fu, C. H. and Sakamoto, K. M. (2007) PEG-asparaginase. Expert Opin. Pharmacother. 8, 1977-1984. https://doi.org/10.1517/14656566.8.12.1977
  31. Galluzzi, L., Kepp, O., Vander Heiden, M. G. and Kroemer, G. (2013) Metabolic targets for cancer therapy. Nat. Rev. Drug Discov. 12, 829-846. https://doi.org/10.1038/nrd4145
  32. Gao, P., Tchernyshyov, I., Chang, T. C., Lee, Y. S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T. and Dang, C. V. (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762-765. https://doi.org/10.1038/nature07823
  33. Garassino, M. C., Marabese, M., Rusconi, P., Rulli, E., Martelli, O., Farina, G., Scanni, A. and Broggini, M. (2011) Different types of KRas mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann. Oncol. 22, 235-237. https://doi.org/10.1093/annonc/mdq680
  34. Gatenby, R. A. and Gillies, R. J. (2004) Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4, 891-899. https://doi.org/10.1038/nrc1478
  35. Glazer, E. S., Piccirillo, M., Albino, V., Di Giacomo, R., Palaia, R., Mastro, A. A., Beneduce, G., Castello, G., De Rosa, V., Petrillo, A., Ascierto, P. A., Curley, S. A. and Izzo, F. (2010) Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. J. Clin. Oncol. 28, 2220-2226.
  36. Go, M. K., Zhang, W. C., Lim, B. and Yew, W. S. (2014) Glycine decarboxylase is an unusual amino acid decarboxylase involved in tumorigenesis. Biochemistry 53, 947-956. https://doi.org/10.1021/bi4014227
  37. Gouw, A. M., Eberlin, L. S., Margulis, K., Sullivan, D. K., Toal, G. G., Tong, L., Zare, R. N. and Felsher, D. W. (2017) Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc. Natl. Acad. Sci. U.S.A. 114, 4300-4305. https://doi.org/10.1073/pnas.1617709114
  38. Gray, L. R., Tompkins, S. C. and Taylor, E. B. (2014) Regulation of pyruvate metabolism and human disease. Cell. Mol. Life Sci. 71, 2577-2604. https://doi.org/10.1007/s00018-013-1539-2
  39. Grewe, M., Gansauge, F., Schmid, R. M., Adler, G. and Seufferlein, T. (1999) Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res. 59, 3581-3587.
  40. Gridelli, C., Rossi, A., Carbone, D. P., Guarize, J., Karachaliou, N., Mok, T., Petrella, F., Spaggiari, L. and Rosell, R. (2015) Non-smallcell lung cancer. Nat. Rev. Dis. Primers 1, 15009.
  41. Hanahan, D. and Weinberg, R. A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013
  42. Haq, R., Shoag, J., Andreu-Perez, P., Yokoyama, S., Edelman, H., Rowe, G. C., Frederick, D. T., Hurley, A. D., Nellore, A., Kung, A. L., Wargo, J. A., Song, J. S., Fisher, D. E., Arany, Z. and Widlund, H. R. (2013) Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF. Cancer Cell 23, 302-315. https://doi.org/10.1016/j.ccr.2013.02.003
  43. Hassanein, M., Qian, J., Hoeksema, M. D., Wang, J., Jacobovitz, M., Ji, X., Harris, F. T., Harris, B. K., Boyd, K. L., Chen, H., Eisenberg, R. and Massion, P. P. (2015) Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int. J. Cancer 137, 1587-1597. https://doi.org/10.1002/ijc.29535
  44. Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A. and Thompson, C. B. (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8, 311-321. https://doi.org/10.1016/j.ccr.2005.09.008
  45. Hensley, C. T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., Wodzak, M., Klimko, C., McMillan, E., Butt, Y., Ni, M., Oliver, D., Torrealba, J., Malloy, C. R., Kernstine, K., Lenkinski, R. E. and DeBerardinis, R. J. (2016) Metabolic heterogeneity in human lung tumors. Cell 164, 681-694. https://doi.org/10.1016/j.cell.2015.12.034
  46. Hobbs, G. A., Der, C. J. and Rossman, K. L. (2016) RAS isoforms and mutations in cancer at a glance. J. Cell Sci. 129, 1287-1292. https://doi.org/10.1242/jcs.182873
  47. Houchens, D. P., Ovejera, A. A., Riblet, S. M. and Slagel, D. E. (1983) Human brain tumor xenografts in nude mice as a chemotherapy model. Eur. J. Cancer Clin. Oncol. 19, 799-805. https://doi.org/10.1016/0277-5379(83)90012-3
  48. Hrustanovic, G., Olivas, V., Pazarentzos, E., Tulpule, A., Asthana, S., Blakely, C. M., Okimoto, R. A., Lin, L., Neel, D. S., Sabnis, A., Flanagan, J., Chan, E., Varella-Garcia, M., Aisner, D. L., Vaishnavi, A., Ou, S. H., Collisson, E. A., Ichihara, E., Mack, P. C., Lovly, C. M., Karachaliou, N., Rosell, R., Riess, J. W., Doebele, R. C. and Bivona, T. G. (2015) RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer. Nat. Med. 21, 1038-1047. https://doi.org/10.1038/nm.3930
  49. Huang, M., Chida, K., Kamata, N., Nose, K., Kato, M., Homma, Y., Takenawa, T. and Kuroki, T. (1988) Enhancement of inositol phospholipid metabolism and activation of protein kinase C in ras-transformed rat fibroblasts. J. Biol. Chem. 263, 17975-17980.
  50. Hunt, T. K., Aslam, R. S., Beckert, S., Wagner, S., Ghani, Q. P., Hussain, M. Z., Roy, S. and Sen, C. K. (2007) Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxid. Redox Signal. 9, 1115-1124. https://doi.org/10.1089/ars.2007.1674
  51. Iurlaro, R., Leon-Annicchiarico, C. L. and Munoz-Pinedo, C. (2014) Regulation of cancer metabolism by oncogenes and tumor suppressors. Methods Enzymol. 542, 59-80.
  52. Izzo, F., Marra, P., Beneduce, G., Castello, G., Vallone, P., De Rosa, V., Cremona, F., Ensor, C. M., Holtsberg, F. W., Bomalaski, J. S., Clark, M. A., Ng, C. and Curley, S. A. (2004) Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J. Clin. Oncol. 22, 1815-1822. https://doi.org/10.1200/JCO.2004.11.120
  53. Jeon, Y. J., Khelifa, S., Ratnikov, B., Scott, D. A., Feng, Y., Parisi, F., Ruller, C., Lau, E., Kim, H., Brill, L. M., Jiang, T., Rimm, D. L., Cardiff, R. D., Mills, G. B., Smith, J. W., Osterman, A. L., Kluger, Y. and Ronai, Z. A. (2015) Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer Cell 27, 354-369. https://doi.org/10.1016/j.ccell.2015.02.006
  54. Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., Liang, M. C., Cai, D., Naumov, G. N., Bao, L., Contreras, C. M., Li, D., Chen, L., Krishnamurthy, J., Koivunen, J., Chirieac, L. R., Padera, R. F., Bronson, R. T., Lindeman, N. I., Christiani, D. C., Lin, X., Shapiro, G. I., Janne, P. A., Johnson, B. E., Meyerson, M., Kwiatkowski, D. J., Castrillon, D. H., Bardeesy, N., Sharpless, N. E. and Wong, K. K. (2007) LKB1 modulates lung cancer differentiation and metastasis. Nature 448, 807-810. https://doi.org/10.1038/nature06030
  55. Katayama, R., Lovly, C. M. and Shaw, A. T. (2015) Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm for precision cancer medicine. Clin. Cancer Res. 21, 2227-2235. https://doi.org/10.1158/1078-0432.CCR-14-2791
  56. Kawada, K., Toda, K. and Sakai, Y. (2017) Targeting metabolic reprogramming in KRAS-driven cancers. Int. J. Clin. Oncol. 22, 651-659. https://doi.org/10.1007/s10147-017-1156-4
  57. Kempf, E., Rousseau, B., Besse, B. and Paz-Ares, L. (2016) KRAS oncogene in lung cancer: focus on molecularly driven clinical trials. Eur. Respir. Rev. 25, 71-76. https://doi.org/10.1183/16000617.0071-2015
  58. Kerr, E. M. and Martins, C. P. (2017) Metabolic rewiring in mutant Kras lung cancer. FEBS J. doi: 10.1111/febs.14125 [Epub ahead of print].
  59. Kim, J., Hu, Z., Cai, L., Li, K., Choi, E., Faubert, B., Bezwada, D., Rodriguez-Canales, J., Villalobos, P., Lin, Y.-F., Ni, M., Huffman, K. E., Girard, L., Byers, L. A., Unsal-Kacmaz, K., Peña, C. G., Heymach, J. V., Wauters, E., Vansteenkiste, J., Castrillon, D. H., Chen, B. P. C., Wistuba, I., Lambrechts, D., Xu, J., Minna, J. D. and DeBerardinis, R. J. (2017) CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature 546, 168-172. https://doi.org/10.1038/nature22359
  60. Kimmelman, A. C. (2015) Metabolic dependencies in RAS-driven cancers. Clin. Cancer Res. 21, 1828-1834.
  61. King, A., Selak, M. A. and Gottlieb, E. (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25, 4675-4682.
  62. Kroemer, G. and Pouyssegur, J. (2008) Tumor cell metabolism: cancer's Achilles' heel. Cancer Cell 13, 472-482. https://doi.org/10.1016/j.ccr.2008.05.005
  63. Kurtzberg, J., Asselin, B., Bernstein, M., Buchanan, G. R., Pollock, B. H. and Camitta, B. M. (2011) Polyethylene glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866). J. Pediatr. Hematol. Oncol. 33, 610-616. https://doi.org/10.1097/MPH.0b013e31822d4d4e
  64. Levine, A. J. and Puzio-Kuter, A. M. (2010) The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330, 1340-1344.
  65. Li, W., Saud, S. M., Young, M. R., Chen, G. and Hua, B. (2015) Targeting AMPK for cancer prevention and treatment. Oncotarget 6, 7365-7378. https://doi.org/10.18632/oncotarget.3629
  66. Lin, J. J. and Shaw, A. T. (2016) Resisting resistance: targeted therapies in lung cancer. Trends Cancer 2, 350-364. https://doi.org/10.1016/j.trecan.2016.05.010
  67. Liu, W., Le, A., Hancock, C., Lane, A. N., Dang, C. V., Fan, T. W. and Phang, J. M. (2012) Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc. Natl. Acad. Sci. U.S.A. 109, 8983-8988. https://doi.org/10.1073/pnas.1203244109
  68. Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., Sasaki, A. T., Anastasiou, D., Mullarky, E., Vokes, N. I., Sasaki, M., Beroukhim, R., Stephanopoulos, G., Ligon, A. H., Meyerson, M., Richardson, A. L., Chin, L., Wagner, G., Asara, J. M., Brugge, J. S., Cantley, L. C. and Vander Heiden, M. G. (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 43, 869-874. https://doi.org/10.1038/ng.890
  69. Lv, J., Wang, J., Chang, S., Liu, M. and Pang, X. (2016) The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism? Acta Biochim. Biophys. Sin. (Shanghai) 48, 17-26.
  70. Lyssiotis, C. A. and Kimmelman, A. C. (2017) Metabolic interactions in the tumor microenvironment. Trends Cell Biol. 27, 863-875. https://doi.org/10.1016/j.tcb.2017.06.003
  71. Magda, D., Lecane, P., Prescott, J., Thiemann, P., Ma, X., Dranchak, P. K., Toleno, D. M., Ramaswamy, K., Siegmund, K. D. and Hacia, J. G. (2008) mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft. BMC Genomics 9, 521. https://doi.org/10.1186/1471-2164-9-521
  72. Mahoney, C. L., Choudhury, B., Davies, H., Edkins, S., Greenman, C., Haaften, G., Mironenko, T., Santarius, T., Stevens, C., Stratton, M. R. and Futreal, P. A. (2009) LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition. Br. J. Cancer 100, 370-375. https://doi.org/10.1038/sj.bjc.6604886
  73. Mailloux, R. J. (2015) Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox Biol. 4, 381-398. https://doi.org/10.1016/j.redox.2015.02.001
  74. Makinoshima, H., Takita, M., Matsumoto, S., Yagishita, A., Owada, S., Esumi, H. and Tsuchihara, K. (2014) Epidermal growth factor receptor (EGFR) signaling regulates global metabolic pathways in EGFR-mutated lung adenocarcinoma. J. Biol. Chem. 289, 20813-20823. https://doi.org/10.1074/jbc.M114.575464
  75. Mannava, S., Grachtchouk, V., Wheeler, L. J., Im, M., Zhuang, D., Slavina, E. G., Mathews, C. K., Shewach, D. S. and Nikiforov, M. A. (2008) Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle 7, 2392-2400. https://doi.org/10.4161/cc.6390
  76. Mao, C., Qiu, L. X., Liao, R. Y., Du, F. B., Ding, H., Yang, W. C., Li, J. and Chen, Q. (2010) KRAS mutations and resistance to EGFRTKIs treatment in patients with non-small cell lung cancer: a metaanalysis of 22 studies. Lung Cancer 69, 272-278. https://doi.org/10.1016/j.lungcan.2009.11.020
  77. Martin-Bernabe, A., Cortes, R., Lehmann, S. G., Seve, M., Cascante, M. and Bourgoin-Voillard, S. (2014) Quantitative proteomic approach to understand metabolic adaptation in non-small cell lung cancer. J. Proteome Res. 13, 4695-4704. https://doi.org/10.1021/pr500327v
  78. Mathers, C. D. and Loncar, D. (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3, e442. https://doi.org/10.1371/journal.pmed.0030442
  79. Mayers, J. R., Torrence, M. E., Danai, L. V., Papagiannakopoulos, T., Davidson, S. M., Bauer, M. R., Lau, A. N., Ji, B. W., Dixit, P. D., Hosios, A. M., Muir, A., Chin, C. R., Freinkman, E., Jacks, T., Wolpin, B. M., Vitkup, D. and Vander Heiden, M. G. (2016) Tissue of origin dictates branched-chain amino acid metabolism in mutant Krasdriven cancers. Science 353, 1161-1165. https://doi.org/10.1126/science.aaf5171
  80. Megchelenbrink, W., Katzir, R., Lu, X., Ruppin, E. and Notebaart, R. A. (2015) Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival. Proc. Natl. Acad. Sci. U.S.A. 112, 12217-12222. https://doi.org/10.1073/pnas.1508573112
  81. Menendez, J. A. and Lupu, R. (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer 7, 763-777.
  82. Meng, D., Yuan, M., Li, X., Chen, L., Yang, J., Zhao, X., Ma, W. and Xin, J. (2013) Prognostic value of K-RAS mutations in patients with non-small cell lung cancer: a systematic review with meta-analysis. Lung Cancer 81, 1-10. https://doi.org/10.1016/j.lungcan.2013.03.019
  83. Migita, T., Narita, T., Nomura, K., Miyagi, E., Inazuka, F., Matsuura, M., Ushijima, M., Mashima, T., Seimiya, H., Satoh, Y., Okumura, S., Nakagawa, K. and Ishikawa, Y. (2008) ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res. 68, 8547-8554.
  84. Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E. and Adjei, A. A. (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin. Proc. 83, 584-594. https://doi.org/10.1016/S0025-6196(11)60735-0
  85. Momcilovic, M., Bailey, S. T., Lee, J. T., Fishbein, M. C., Magyar, C., Braas, D., Graeber, T., Jackson, N. J., Czernin, J., Emberley, E., Gross, M., Janes, J., Mackinnon, A., Pan, A., Rodriguez, M., Works, M., Zhang, W., Parlati, F., Demo, S., Garon, E., Krysan, K., Walser, T. C., Dubinett, S. M., Sadeghi, S., Christofk, H. R. and Shackelford, D. B. (2017) Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer. Cell Rep. 18, 601-610. https://doi.org/10.1016/j.celrep.2016.12.061
  86. Mondesir, J., Willekens, C., Touat, M. and de Botton, S. (2016) IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives. J. Blood Med. 7, 171-180. https://doi.org/10.2147/JBM.S70716
  87. Moran, D. M., Trusk, P. B., Pry, K., Paz, K., Sidransky, D. and Bacus, S. S. (2014) KRAS mutation status is associated with enhanced dependency on folate metabolism pathways in non-small cell lung cancer cells. Mol. Cancer Ther. 13, 1611-1624.
  88. Nagarajan, A., Malvi, P. and Wajapeyee, N. (2016) Oncogene-directed alterations in cancer cell metabolism. Trends Cancer 2, 365-377. https://doi.org/10.1016/j.trecan.2016.06.002
  89. Newman, A. C. and Maddocks, O. D. K. (2017) One-carbon metabolism in cancer. Br. J. Cancer 116, 1499-1504. https://doi.org/10.1038/bjc.2017.118
  90. Onetti, R., Baulida, J. and Bassols, A. (1997) Increased glucose transport in ras-transformed fibroblasts: a possible role for N-glycosylation of GLUT1. FEBS Lett. 407, 267-270. https://doi.org/10.1016/S0014-5793(97)00340-2
  91. Ott, P. A., Carvajal, R. D., Pandit-Taskar, N., Jungbluth, A. A., Hoffman, E. W., Wu, B. W., Bomalaski, J. S., Venhaus, R., Pan, L., Old, L. J., Pavlick, A. C. and Wolchok, J. D. (2013) Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma. Invest. New Drugs 31, 425-434.
  92. Pakala, R., Kreisel, M. and Bachrach, U. (1988) Polyamine metabolism and interconversion in NIH 3T3 and ras-transfected NIH 3T3 cells. Cancer Res. 48, 3336-3340.
  93. Pao, W. and Miller, V. A. (2005) Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J. Clin. Oncol. 23, 2556-2568. https://doi.org/10.1200/JCO.2005.07.799
  94. Parker, S. J. and Metallo, C. M. (2015) Metabolic consequences of oncogenic IDH mutations. Pharmacol. Ther. 152, 54-62. https://doi.org/10.1016/j.pharmthera.2015.05.003
  95. Pavlova, N. N. and Thompson, C. B. (2016) The emerging hallmarks of cancer metabolism. Cell Metab. 23, 27-47. https://doi.org/10.1016/j.cmet.2015.12.006
  96. Pikor, L. A., Ramnarine, V. R., Lam, S. and Lam, W. L. (2013) Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer 82, 179-189. https://doi.org/10.1016/j.lungcan.2013.07.025
  97. Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H. K., Jang, H. G., Jha, A. K., Chen, W. W., Barrett, F. G., Stransky, N., Tsun, Z. Y., Cowley, G. S., Barretina, J., Kalaany, N. Y., Hsu, P. P., Ottina, K., Chan, A. M., Yuan, B., Garraway, L. A., Root, D. E., Mino-Kenudson, M., Brachtel, E. F., Driggers, E. M. and Sabatini, D. M. (2011) Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346-350. https://doi.org/10.1038/nature10350
  98. Pusch, O., Soucek, T., Hengstschlager-Ottnad, E., Bernaschek, G. and Hengstschlager, M. (1997) Cellular targets for activation by c-Myc include the DNA metabolism enzyme thymidine kinase. DNA Cell Biol. 16, 737-747.
  99. Pylayeva-Gupta, Y., Grabocka, E. and Bar-Sagi, D. (2011) RAS oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer 11, 761-774. https://doi.org/10.1038/nrc3106
  100. Quail, D. F. and Joyce, J. A. (2013) Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423-1437. https://doi.org/10.1038/nm.3394
  101. Ramirez de Molina, A., Rodriguez-Gonzalez, A., Gutierrez, R., Martinez-Pineiro, L., Sanchez, J., Bonilla, F., Rosell, R. and Lacal, J. (2002) Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem. Biophys. Res. Commun. 296, 580-583. https://doi.org/10.1016/S0006-291X(02)00920-8
  102. Renaud, S., Falcoz, P. E., Schaeffer, M., Guenot, D., Romain, B., Olland, A., Reeb, J., Santelmo, N., Chenard, M. P., Legrain, M., Voegeli, A. C., Beau-Faller, M. and Massard, G. (2015) Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases. Br. J. Cancer 113, 1206-1215. https://doi.org/10.1038/bjc.2015.327
  103. Roberts, P. J. and Stinchcombe, T. E. (2013) KRAS mutation: should we test for it, and does it matter? J. Clin. Oncol. 31, 1112-1121. https://doi.org/10.1200/JCO.2012.43.0454
  104. Saintigny, P. and Burger, J. A. (2012) Recent advances in non-small cell lung cancer biology and clinical management. Discov. Med. 13, 287-297.
  105. Saito, T., Chiba, T., Yuki, K., Zen, Y., Oshima, M., Koide, S., Motoyama, T., Ogasawara, S., Suzuki, E., Ooka, Y., Tawada, A., Tada, M., Kanai, F., Takiguchi, Y., Iwama, A. and Yokosuka, O. (2013) Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells. PLoS ONE 8, e70010. https://doi.org/10.1371/journal.pone.0070010
  106. Sanchez-Cespedes, M., Parrella, P., Esteller, M., Nomoto, S., Trink, B., Engles, J. M., Westra, W. H., Herman, J. G. and Sidransky, D. (2002) Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res. 62, 3659-3662.
  107. Scott, D. A., Richardson, A. D., Filipp, F. V., Knutzen, C. A., Chiang, G. G., Ronai, Z. A., Osterman, A. L. and Smith, J. W. (2011) Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J. Biol. Chem. 286, 42626-42634. https://doi.org/10.1074/jbc.M111.282046
  108. Sellers, K., Fox, M. P., Bousamra, M., 2nd, Slone, S. P., Higashi, R. M., Miller, D. M., Wang, Y., Yan, J., Yuneva, M. O., Deshpande, R., Lane, A. N. and Fan, T. W. (2015) Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J. Clin. Invest. 125, 687-698. https://doi.org/10.1172/JCI72873
  109. Shackelford, D. B., Abt, E., Gerken, L., Vasquez, D. S., Seki, A., Leblanc, M., Wei, L., Fishbein, M. C., Czernin, J., Mischel, P. S. and Shaw, R. J. (2013) LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell 23, 143-158. https://doi.org/10.1016/j.ccr.2012.12.008
  110. Shackelford, D. B. and Shaw, R. J. (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563-575. https://doi.org/10.1038/nrc2676
  111. Shim, H., Dolde, C., Lewis, B. C., Wu, C. S., Dang, G., Jungmann, R. A., Dalla-Favera, R. and Dang, C. V. (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl. Acad. Sci. U.S.A. 94, 6658-6663. https://doi.org/10.1073/pnas.94.13.6658
  112. Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C. and Kimmelman, A. C. (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496, 101-105. https://doi.org/10.1038/nature12040
  113. Spees, J. L., Olson, S. D., Whitney, M. J. and Prockop, D. J. (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. U.S.A. 103, 1283-1288. https://doi.org/10.1073/pnas.0510511103
  114. Stolze, B., Reinhart, S., Bulllinger, L., Frohling, S. and Scholl, C. (2015) Comparative analysis of KRAS codon 12, 13, 18, 61, and 117 mutations using human MCF10A isogenic cell lines. Sci. Rep. 5, 8535. https://doi.org/10.1038/srep08535
  115. Storozhuk, Y., Hopmans, S. N., Sanli, T., Barron, C., Tsiani, E., Cutz, J. C., Pond, G., Wright, J., Singh, G. and Tsakiridis, T. (2013) Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br. J. Cancer 108, 2021-2032. https://doi.org/10.1038/bjc.2013.187
  116. Svensson, R. U., Parker, S. J., Eichner, L. J., Kolar, M. J., Wallace, M., Brun, S. N., Lombardo, P. S., Van Nostrand, J. L., Hutchins, A., Vera, L., Gerken, L., Greenwood, J., Bhat, S., Harriman, G., Westlin, W. F., Harwood, H. J., Jr., Saghatelian, A., Kapeller, R., Metallo, C. M. and Shaw, R. J. (2016) Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat. Med. 22, 1108-1119. https://doi.org/10.1038/nm.4181
  117. Svensson, R. U. and Shaw, R. J. (2016) Lipid synthesis is a metabolic liability of non-small cell lung cancer. Cold Spring Harb. Symp. Quant. Biol. 81, 93-103. https://doi.org/10.1101/sqb.2016.81.030874
  118. Swanton, C. and Govindan, R. (2016) Clinical implications of genomic discoveries in lung cancer. N. Engl. J. Med. 374, 1864-1873. https://doi.org/10.1056/NEJMra1504688
  119. Swietach, P., Vaughan-Jones, R. D. and Harris, A. L. (2007) Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metastasis Rev. 26, 299-310.
  120. Taylor, C. W., Dorr, R. T., Fanta, P., Hersh, E. M. and Salmon, S. E. (2001) A phase I and pharmacodynamic evaluation of polyethylene glycol-conjugated L-asparaginase in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 47, 83-88. https://doi.org/10.1007/s002800000207
  121. Tennant, D. A., Duran, R. V. and Gottlieb, E. (2010) Targeting metabolic transformation for cancer therapy. Nat. Rev. Cancer 10, 267-277. https://doi.org/10.1038/nrc2817
  122. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J. and Jemal, A. (2015) Global cancer statistics, 2012. CA Cancer J. Clin. 65, 87-108.
  123. Tsun, Z. Y. and Possemato, R. (2015) Amino acid management in cancer. Semin. Cell Dev. Biol. 43, 22-32. https://doi.org/10.1016/j.semcdb.2015.08.002
  124. Vignot, S., Faivre, S., Aguirre, D. and Raymond, E. (2005) mTORtargeted therapy of cancer with rapamycin derivatives. Ann. Oncol. 16, 525-537. https://doi.org/10.1093/annonc/mdi113
  125. Wallace, D. C. (2012) Mitochondria and cancer. Nat. Rev. Cancer 12, 685-698. https://doi.org/10.1038/nrc3365
  126. Wang, H. Q., Altomare, D. A., Skele, K. L., Poulikakos, P. I., Kuhajda, F. P., Di Cristofano, A. and Testa, J. R. (2005) Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells. Oncogene 24, 3574-3582. https://doi.org/10.1038/sj.onc.1208463
  127. Warburg, O. (1956) On the origin of cancer cells. Science 123, 309-314. https://doi.org/10.1126/science.123.3191.309
  128. Weinberg, F., Hamanaka, R., Wheaton, W. W., Weinberg, S., Joseph, J., Lopez, M., Kalyanaraman, B., Mutlu, G. M., Budinger, G. R. and Chandel, N. S. (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl. Acad. Sci. U.S.A. 107, 8788-8793. https://doi.org/10.1073/pnas.1003428107
  129. Whang, Y. M., Park, S. I., Trenary, I. A., Egnatchik, R. A., Fessel, J. P., Kaufman, J. M., Carbone, D. P. and Young, J. D. (2016) LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small-cell lung cancer (NSCLC) cells. Oncogene 35, 856-866. https://doi.org/10.1038/onc.2015.140
  130. Whitaker-Menezes, D., Martinez-Outschoorn, U. E., Flomenberg, N., Birbe, R. C., Witkiewicz, A. K., Howell, A., Pavlides, S., Tsirigos, A., Ertel, A., Pestell, R. G., Broda, P., Minetti, C., Lisanti, M. P. and Sotgia, F. (2011) Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle 10, 4047-4064. https://doi.org/10.4161/cc.10.23.18151
  131. Wick, A. N., Drury, D. R., Nakada, H. I. and Wolfe, J. B. (1957) Localization of the primary metabolic block produced by 2-deoxyglucose. J. Biol. Chem. 224, 963-969.
  132. Wise, D. R. and Thompson, C. B. (2010) Glutamine addiction: a new therapeutic target in cancer. Trends Biochem. Sci. 35, 427-433. https://doi.org/10.1016/j.tibs.2010.05.003
  133. Wu, R., Galan-Acosta, L. and Norberg, E. (2015) Glucose metabolism provide distinct prosurvival benefits to non-small cell lung carcinomas. Biochem. Biophys. Res. Commun. 460, 572-577.
  134. Yang, T. S., Lu, S. N., Chao, Y., Sheen, I. S., Lin, C. C., Wang, T. E., Chen, S. C., Wang, J. H., Liao, L. Y., Thomson, J. A., Wang-Peng, J., Chen, P. J. and Chen, L. T. (2010) A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients. Br. J. Cancer 103, 954-960. https://doi.org/10.1038/sj.bjc.6605856
  135. Yau, T., Cheng, P. N., Chan, P., Chan, W., Chen, L., Yuen, J., Pang, R., Fan, S. T. and Poon, R. T. (2013) A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma. Invest. New Drugs 31, 99-107.
  136. Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., Yan, H., Wang, W., Chen, S., Viale, A., Zheng, H., Paik, J. H., Lim, C., Guimaraes, A. R., Martin, E. S., Chang, J., Hezel, A. F., Perry, S. R., Hu, J., Gan, B., Xiao, Y., Asara, J. M., Weissleder, R., Wang, Y. A., Chin, L., Cantley, L. C. and DePinho, R. A. (2012) Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149, 656-670. https://doi.org/10.1016/j.cell.2012.01.058
  137. Yuneva, M. O., Fan, T. W., Allen, T. D., Higashi, R. M., Ferraris, D. V., Tsukamoto, T., Mates, J. M., Alonso, F. J., Wang, C., Seo, Y., Chen, X. and Bishop, J. M. (2012) The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 15, 157-170. https://doi.org/10.1016/j.cmet.2011.12.015
  138. Zhang, J., Fan, J., Venneti, S., Cross, J. R., Takagi, T., Bhinder, B., Djaballah, H., Kanai, M., Cheng, E. H., Judkins, A. R., Pawel, B., Baggs, J., Cherry, S., Rabinowitz, J. D. and Thompson, C. B. (2014a) Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol. Cell 56, 205-218. https://doi.org/10.1016/j.molcel.2014.08.018
  139. Zhang, J., Song, F., Zhao, X., Jiang, H., Wu, X., Wang, B., Zhou, M., Tian, M., Shi, B., Wang, H., Jia, Y., Wang, H., Pan, X. and Li, Z. (2017) EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer. Mol. Cancer 16, 127. https://doi.org/10.1186/s12943-017-0704-x
  140. Zhang, W. C., Shyh-Chang, N., Yang, H., Rai, A., Umashankar, S., Ma, S., Soh, B. S., Sun, L. L., Tai, B. C., Nga, M. E., Bhakoo, K. K., Jayapal, S. R., Nichane, M., Yu, Q., Ahmed, D. A., Tan, C., Sing, W. P., Tam, J., Thirugananam, A., Noghabi, M. S., Pang, Y. H., Ang, H. S., Mitchell, W., Robson, P., Kaldis, P., Soo, R. A., Swarup, S., Lim, E. H. and Lim, B. (2012) Glycine decarboxylase activity drives nonsmall cell lung cancer tumor-initiating cells and tumorigenesis. Cell 148, 259-272. https://doi.org/10.1016/j.cell.2011.11.050
  141. Zhang, Y., Storr, S. J., Johnson, K., Green, A. R., Rakha, E. A., Ellis, I. O., Morgan, D. A. and Martin, S. G. (2014b) Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy. Oncotarget 5, 12936-12949.
  142. Zhang, Z., Stiegler, A. L., Boggon, T. J., Kobayashi, S. and Halmos, B. (2010) EGFR-mutated lung cancer: a paradigm of molecular oncology. Oncotarget 1, 497-514.

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