Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Metastasis Awakening: The challenges of targeting minimal residual cancer

Cancer resistance to targeted therapies seems to be a field of active research. But there are still open questions as to what drives drug resistance not only in metastatic tumor cells but also in disseminated tumor cells (DTCs) during adjuvant treatment, before metastases are established in other organs. Targeting this residual cancer disease or keeping these DTCs in a dormant state may be a way to stop progression to metastatic disease. For this, a further understanding of the biology of these cells is necessary. In 'Bedside to Bench', Bernhard Polzer and Christopher Klein put forward several scenarios to explain the different resistant mechanisms that might account for DTCs unresponsiveness to cancer drugs and emphasize the relevance of synchronizing targeted therapies with the changing responsive or dormant state of disseminated cancer cells in the clinic. In 'Bench to Bedside', Julio A Aguirre-Ghiso, Paloma Bragado and Maria Soledad Sosa discuss possible cell-intrinsic and microenvironment-derived signaling pathways that may be exploited to maintain dormancy in DTCs and explore the possibility of using dormancy gene signatures to identify individuals with dormant disease.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Genetic heterogeneity and various cellular states may account for differences in drug response in early compared to late systemic cancer.

Marina Corral


  1. Douillard, J.Y. et al. J. Clin. Oncol. 28, 4697–4705 (2010).

    CAS  Article  Google Scholar 

  2. Slamon, D.J. et al. N. Engl. J. Med. 344, 783–792 (2001).

    CAS  Article  Google Scholar 

  3. Sosman, J.A. et al. N. Engl. J. Med. 366, 707–714 (2012).

    CAS  Article  Google Scholar 

  4. Mok, T.S. et al. N. Engl. J. Med. 361, 947–957 (2009).

    CAS  Article  Google Scholar 

  5. Gianni, L. et al. Lancet Oncol. 12, 236–244 (2011).

    CAS  Article  Google Scholar 

  6. Alberts, S.R. et al. J. Am. Med. Assoc. 307, 1383–1393 (2012).

    CAS  Article  Google Scholar 

  7. Goss, G.D. et al. J. Clin. Oncol. 28, Suppl 18s, LBA7005 (2010).

    Article  Google Scholar 

  8. Sullivan, R.J. & Flaherty, K.T. Eur. J. Cancer published online, doi:10.1016/j.ejca.2012.11.019 (2 January 2013).

  9. Liu, D., Aguirre Ghiso, J., Estrada, Y. & Ossowski, L. Cancer Cell 1, 445–457 (2002).

    CAS  Article  Google Scholar 

  10. Adam, A.P. et al. Cancer Res. 69, 5664–5672 (2009).

    CAS  Article  Google Scholar 

  11. Stoecklein, N.H. & Klein, C.A. Int. J. Cancer 126, 589–598 (2010).

    CAS  Article  Google Scholar 

  12. Gow, C.H. et al. Ann. Oncol. 20, 696–702 (2009).

    Article  Google Scholar 

  13. Schardt, J.A. et al. Cancer Cell 8, 227–239 (2005).

    CAS  Article  Google Scholar 

  14. Dent, R. et al. Clin. Cancer Res. 13, 4429–4434 (2007).

    Article  Google Scholar 

  15. Bouwman, P. et al. Nat. Struct. Mol. Biol. 17, 688–695 (2010).

    CAS  Article  Google Scholar 

  16. Gerlinger, M. et al. N. Engl. J. Med. 366, 883–892 (2012).

    CAS  Article  Google Scholar 

  17. Nik-Zainal, S. et al. Cell 149, 994–1007 (2012).

    CAS  Article  Google Scholar 

Download references


We apologize to all colleagues whose work could not be cited because of space limitations. This work was supported by grants from the Dr. Josef Steiner Cancer Foundation and the Bavarian Ministry of Trade and Industry.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Christoph A Klein.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Polzer, B., Klein, C. Metastasis Awakening: The challenges of targeting minimal residual cancer. Nat Med 19, 274–275 (2013).

Download citation

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing