Untuning the tumor metabolic machine: Targeting cancer metabolism: a bedside lesson

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Several decades of scientific observations followed by years of basic and now clinical research support the notion that the metabolic power of tumor cells can provide the long-desired Achilles' heel of cancer. Yet many questions remain as to what defines the true metabolic makeup of a tumor and whether well-known factors and pathways involved in metabolic signaling act as tumor suppressors or oncogenes. In 'Bedside to Bench', Kıvanç Birsoy, David M. Sabatini and Richard Possemato discuss how retrospective studies of diabetic individuals with pancreatic cancer treated with the antidiabetic drug metformin point to a possible anticancer effect for this drug. Further research will need to discern whether this drug acts at the organismal level or by directly targeting the power plant of tumor cells. In 'Bench to Bedside', Regina M. Young and M. Celeste Simon peruse the complex function of a key metabolic factor that mediates the cell's response to low oxygen levels, often found in tumors. This hypoxia-inducible factor (HIF) comes in two flavors, which can be either tumor promoting or tumor suppressive, depending on the type of cancer. Because of this, the therapeutic use of HIF inhibitors must proceed with caution. Further defining the relationship between metabolic regulation of HIF and tumor progression may open up new diagnostic tools and treatments.

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Figure 1: Potential effects of metformin on tumor growth.

References

  1. 1

    Ward, P.S. & Thompson, C.B. Cancer Cell 21, 297–308 (2012).

  2. 2

    Eng, C., Kiuru, M., Fernandez, M.J. & Aaltonen, L.A. Nat. Rev. Cancer 3, 193–202 (2003).

  3. 3

    Dang, L., Jin, S. & Su, S.M. Trends Mol. Med. 16, 387–397 (2010).

  4. 4

    Possemato, R. et al. Nature 476, 346–350 (2011).

  5. 5

    Jain, M. et al. Science 336, 1040–1044 (2012).

  6. 6

    DeBerardinis, R.J., Lum, J.J., Hatzivassiliou, G. & Thompson, C.B. Cell Metab. 7, 11–20 (2008).

  7. 7

    Sanli, Y. et al. Ann. Nucl. Med. 26, 345–350 (2012).

  8. 8

    Kalaany, N.Y. & Sabatini, D.M. Nature 458, 725–731 (2009).

  9. 9

    Seyfried, B.T., Kiebish, M., Marsh, J. & Mukherjee, P. J. Cancer Res. Ther. 5 Suppl 1, S7–S15 (2009).

  10. 10

    Broome, J.D. Cancer Treat. Rep. 65 Suppl 4, 111–114 (1981).

  11. 11

    Pelicano, H., Martin, D.S., Xu, R.H. & Huang, P. Oncogene 25, 4633–4646 (2006).

  12. 12

    Sadeghi, N., Abbruzzese, J.L., Yeung, S.C., Hassan, M. & Li, D. Clin. Cancer Res. 18, 2905–2912 (2012).

  13. 13

    Decensi, A. et al. Cancer Prev. Res. (Phila.) 3, 1451–1461 (2010).

  14. 14

    Buzzai, M. et al. Cancer Res. 67, 6745–6752 (2007).

  15. 15

    Bailey, C.J. & Turner, R.C. N. Engl. J. Med. 334, 574–579 (1996).

  16. 16

    Zhou, G. et al. J. Clin. Invest. 108, 1167–1174 (2001).

  17. 17

    Shaw, R.J. et al. Proc. Natl. Acad. Sci. USA 101, 3329–3335 (2004).

  18. 18

    Clark, R.A. & Pavlis, M. J. Invest. Dermatol. 129, 529–531 (2009).

  19. 19

    Hawley, S.A., Gadalla, A.E., Olsen, G.S. & Hardie, D.G. Diabetes 51, 2420–2425 (2002).

  20. 20

    Schneider, M.B. et al. Gastroenterology 120, 1263–1270 (2001).

  21. 21

    Marin-Valencia, I. et al. Cell Metab. 15, 827–837 (2012).

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Correspondence to Richard Possemato.

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