Skip to main content

Advertisement

Log in

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

  • Between Bedside and Bench
  • Published:

From Nature Medicine

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1: Potential effects of metformin on tumor growth.

References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Possemato.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Birsoy, K., Sabatini, D. & Possemato, R. Untuning the tumor metabolic machine: Targeting cancer metabolism: a bedside lesson. Nat Med 18, 1022–1023 (2012). https://doi.org/10.1038/nm.2870

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.2870

  • Springer Nature America, Inc.

This article is cited by

Navigation