DOI QR코드

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Cancer Metabolism: Strategic Diversion from Targeting Cancer Drivers to Targeting Cancer Suppliers

  • Kim, Soo-Youl (Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
  • 투고 : 2015.01.23
  • 심사 : 2015.02.11
  • 발행 : 2015.03.01

초록

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

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참고문헌

  1. Arduino, L. J. and Mellinger, G. T. (1967) Clinical trial of busulfan (NSC-750) in advanced carcinoma of prostate. Cancer Chemother. Rep. 51, 295-303.
  2. Armour, A. A. and Watkins, C. L. (2010) The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer. Eur. Respir. Rev. 19, 186-196. https://doi.org/10.1183/09059180.00005110
  3. Ben Sahra, I., Laurent, K., Loubat, A., Giorgetti-Peraldi, S., Colosetti, P., Auberger, P., Tanti, J. F., Le Marchand-Brustel, Y. and Bost, F. (2008) The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 27, 3576-3586. https://doi.org/10.1038/sj.onc.1211024
  4. Bernards, R. (2012) A missing link in genotype-directed cancer therapy. Cell 151, 465-468. https://doi.org/10.1016/j.cell.2012.10.014
  5. Birsoy, K., Wang, T., Possemato, R., Yilmaz, O. H., Koch, C. E., Chen, W. W., Hutchins, A. W., Gultekin, Y., Peterson, T. R., Carette, J. E., Brummelkamp, T. R., Clish, C. B. and Sabatini, D. M. (2013) MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. Nat. Genet. 45, 104-108.
  6. Brook, J., Bateman, J. R. and Steinfeld, J. L. (1964) Evaluation of Melphalan (Nsc-8806) in Treatment of Multiple Myeloma. Cancer Chemother. Rep. 36, 25-34.
  7. Buck, E., Eyzaguirre, A., Haley, J. D., Gibson, N. W., Cagnoni, P. and Iwata, K. K. (2006) Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity. Mol. Cancer Ther. 5, 2051-2059. https://doi.org/10.1158/1535-7163.MCT-06-0007
  8. Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70. https://doi.org/10.1038/nature11412
  9. Chabner, B. A. and Roberts, T. G., Jr. (2005) Timeline: Chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65-72. https://doi.org/10.1038/nrc1529
  10. Chan, S. (2004) Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. Br. J. Cancer 91, 1420-1424. https://doi.org/10.1038/sj.bjc.6602162
  11. Cheong, H., Lu, C., Lindsten, T. and Thompson, C. B. (2012) Therapeutic targets in cancer cell metabolism and autophagy. Nat. Biotechnol. 30, 671-678. https://doi.org/10.1038/nbt.2285
  12. DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S. and Thompson, C. B. (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad. Sci. U.S.A. 104, 19345-19350. https://doi.org/10.1073/pnas.0709747104
  13. Edmonson, J. H., Lagakos, S., Stolbach, L., Perlia, C. P., Bennett, J. M., Mansour, E. G., Horton, J., Regelson, W., Cummings, F. J., Israel, L., Brodsky, I., Shnider, B. I., Creech, R. and Carbone, P. P. (1976) Mechlorethamine (NSC-762) plus CCNU (NSC-79037) in the treatment of inoperable squamous and large cell carcinoma of the lung. Cancer Treat. Rep. 60, 625-627.
  14. Ertmer, A., Huber, V., Gilch, S., Yoshimori, T., Erfle, V., Duyster, J., Elsasser, H. P. and Schatzl, H. M. (2007) The anticancer drug imatinib induces cellular autophagy. Leukemia 21, 936-942.
  15. Evans, J. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R. and Morris, A. D. (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330, 1304-1305. https://doi.org/10.1136/bmj.38415.708634.F7
  16. Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B. and Rabinowitz, J. D. (2014) Quantitative flux analysis reveals folatedependent NADPH production. Nature 510, 298-302. https://doi.org/10.1038/nature13236
  17. Fausel, C. (2007) Targeted chronic myeloid leukemia therapy: Seeking a cure. Am. J. Health Syst. Pharm. 64, S9-15.
  18. Fisher, B. K. and Elliott, G. B. (1965) Triple drug therapy with actinomycin D (Nsc-3053), chlorambucil (Nsc-3088), and methotrexate (Nsc-740) in metastatic solid tumors in children. Cancer Chemother. Rep. 45, 45-51.
  19. Foley, J. F. and Kennedy, B. J. (1964) Effect of cyclophosphamide (Nsc-26271) on far-advanced neoplasia. Cancer Chemother. Rep. 34, 55-58.
  20. Gilman, A. (1963) The initial clinical trial of nitrogen mustard. Am. J. Surg. 105, 574-578. https://doi.org/10.1016/0002-9610(63)90232-0
  21. Goldman, J. M. and Melo, J. V. (2003) Chronic myeloid leukemia-- advances in biology and new approaches to treatment. N. Engl. J. Med. 349, 1451-1464. https://doi.org/10.1056/NEJMra020777
  22. Gorzalczany, Y., Gilad, Y., Amihai, D., Hammel, I., Sagi-Eisenberg, R. and Merimsky, O. (2011) Combining an EGFR directed tyrosine kinase inhibitor with autophagy-inducing drugs: a beneficial strategy to combat non-small cell lung cancer. Cancer Lett. 310, 207-215. https://doi.org/10.1016/j.canlet.2011.07.002
  23. Haugrud, A. B., Zhuang, Y., Coppock, J. D. and Miskimins, W. K. (2014) Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells. Breast Cancer Res. Treat. 147, 539-550. https://doi.org/10.1007/s10549-014-3128-y
  24. Hay, N. and Sonenberg, N. (2004) Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945. https://doi.org/10.1101/gad.1212704
  25. Jackson, R. C. (1987) Unresolved issues in the biochemical pharmacology of antifolates. NCI Monogr. 9-15.
  26. Jacobs, E. M., Peters, F. C., Luce, J. K., Zippin, C. and Wood, D. A. (1968) Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA 203, 392-398. https://doi.org/10.1001/jama.1968.03140060016005
  27. Janku, F., McConkey, D. J., Hong, D. S. and Kurzrock, R. (2011) Autophagy as a target for anticancer therapy. Nat. Rev. Clin. Oncol. 8, 528-539. https://doi.org/10.1038/nrclinonc.2011.71
  28. Jiralerspong, S., Palla, S. L., Giordano, S. H., Meric-Bernstam, F., Liedtke, C., Barnett, C. M., Hsu, L., Hung, M. C., Hortobagyi, G. N. and Gonzalez-Angulo, A. M. (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J. Clin. Oncol. 27, 3297-3302. https://doi.org/10.1200/JCO.2009.19.6410
  29. Kanzawa, T., Germano, I. M., Komata, T., Ito, H., Kondo, Y. and Kondo, S. (2004) Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 11, 448-457. https://doi.org/10.1038/sj.cdd.4401359
  30. Kimura, T., Takabatake, Y., Takahashi, A. and Isaka, Y. (2013) Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer Res. 73, 3-7.
  31. Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo- Arozena, A. and Adeli, K., et al. (2012) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8, 445-544. https://doi.org/10.4161/auto.19496
  32. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C. and Baldwin, J., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860-921. https://doi.org/10.1038/35057062
  33. Lottmann, H. B., Margaryan, M., Bernuy, M., Rouffet, M. J., Bau, M. O., El-Ghoneimi, A., Aigrain, Y., Stenberg, A. and Lackgren, G. (2002) The effect of endoscopic injections of dextranomer based implants on continence and bladder capacity: a prospective study of 31 patients. J. Urol. 168, 1863-1867. https://doi.org/10.1016/S0022-5347(05)64431-X
  34. Michelakis, E. D., Webster, L. and Mackey, J. R. (2008) Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer 99, 989-994. https://doi.org/10.1038/sj.bjc.6604554
  35. Nieman, K. M., Kenny, H. A., Penicka, C. V., Ladanyi, A., Buell-Gutbrod, R., Zillhardt, M. R., Romero, I. L., Carey, M. S., Mills, G. B., Hotamisligil, G. S., Yamada, S. D., Peter, M. E., Gwin, K. and Lengyel, E. (2011) Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498-1503. https://doi.org/10.1038/nm.2492
  36. Regelson, W., Holland, J. F., Frei, E., 3rd, Gold, G. L., Hall, T., Krant, M. and Miller, S. O. (1964) Comparative clinical toxicity of 6-mercaptopurine (Nsc-755)-1 and 6-mercaptopurine ribonucleoside (Nsc-4911)-2 administered intravenously to patients with advanced cancer. Cancer Chemother. Rep. 36, 41-48.
  37. Robinson, M. M., McBryant, S. J., Tsukamoto, T., Rojas, C., Ferraris, D. V., Hamilton, S. K., Hansen, J. C. and Curthoys, N. P. (2007) Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES). Biochem. J. 406, 407-414. https://doi.org/10.1042/BJ20070039
  38. Sausville, E. A. and Johnson, J. I. (2000) Molecules for the millennium: how will they look? New drug discovery year 2000. Br. J. Cancer 83, 1401-1404. https://doi.org/10.1054/bjoc.2000.1473
  39. Seltzer, M. J., Bennett, B. D., Joshi, A. D., Gao, P., Thomas, A. G., Ferraris, D. V., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Rabinowitz, J. D., Dang, C. V. and Riggins, G. J. (2010) Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 70, 8981-8987. https://doi.org/10.1158/0008-5472.CAN-10-1666
  40. Sonveaux, P., Copetti, T., De Saedeleer, C. J., Vegran, F., Verrax, J., Kennedy, K. M., Moon, E. J., Dhup, S., Danhier, P., Frerart, F., Gallez, B., Ribeiro, A., Michiels, C., Dewhirst, M. W. and Feron, O. (2012) Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PloS One 7, e33418. https://doi.org/10.1371/journal.pone.0033418
  41. Sonveaux, P., Vegran, F., Schroeder, T., Wergin, M. C., Verrax, J., Rabbani, Z. N., De Saedeleer, C. J., Kennedy, K. M., Diepart, C., Jordan, B. F., Kelley, M. J., Gallez, B., Wahl, M. L., Feron, O. and Dewhirst, M. W. (2008) Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J. Clin. Invest. 118, 3930-3942.
  42. Sooparb, S., Price, S. R., Shaoguang, J. and Franch, H. A. (2004) Suppression of chaperone-mediated autophagy in the renal cortex during acute diabetes mellitus. Kidney Int. 65, 2135-2144. https://doi.org/10.1111/j.1523-1755.2004.00639.x
  43. Spear, B. B., Heath-Chiozzi, M. and Huff, J. (2001) Clinical application of pharmacogenetics. Trends Mol. Med. 7, 201-204. https://doi.org/10.1016/S1471-4914(01)01986-4
  44. Stegmeier, F., Warmuth, M., Sellers, W. R. and Dorsch, M. (2010) Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clin. Pharmacol. Ther. 87, 543-552. https://doi.org/10.1038/clpt.2009.297
  45. Strausberg, R. L., Simpson, A. J., Old, L. J. and Riggins, G. J. (2004) Oncogenomics and the development of new cancer therapies. Nature 429, 469-474. https://doi.org/10.1038/nature02627
  46. Takeuchi, H., Kondo, Y., Fujiwara, K., Kanzawa, T., Aoki, H., Mills, G. B. and Kondo, S. (2005) Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res. 65, 3336-3346.
  47. Vander Heiden, M. G. (2011) Targeting cancer metabolism: a therapeutic window opens. Nature reviews. Nat. Rev. Drug Discov. 10, 671-684. https://doi.org/10.1038/nrd3504
  48. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J. and Sutton, G. G., et al. (2001) The sequence of the human genome. Science 291, 1304-1351. https://doi.org/10.1126/science.1058040
  49. Ward, P. S. and Thompson, C. B. (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21, 297-308. https://doi.org/10.1016/j.ccr.2012.02.014
  50. Wilhelm, S. M., Adnane, L., Newell, P., Villanueva, A., Llovet, J. M. and Lynch, M. (2008) Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol. Cancer Ther. 7, 3129-3140. https://doi.org/10.1158/1535-7163.MCT-08-0013
  51. Yun, M., Bang, S. H., Kim, J. W., Park, J. Y., Kim, K. S. and Lee, J. D. (2009) The importance of acetyl coenzyme A synthetase for 11Cacetate uptake and cell survival in hepatocellular carcinoma. J. Nucl. Med. 50, 1222-1228. https://doi.org/10.2967/jnumed.109.062703
  52. Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N. and Pollak, M. (2006) Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66, 10269-10273. https://doi.org/10.1158/0008-5472.CAN-06-1500
  53. Zhao, Y., Liu, H., Riker, A. I., Fodstad, O., Ledoux, S. P., Wilson, G. L. and Tan, M. (2011) Emerging metabolic targets in cancer therapy. Front. Biosci. 16, 1844-1860. https://doi.org/10.2741/3826

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