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Metastasis Awakening: The challenges of targeting minimal residual cancer

Nature Medicine volume 19, pages 274–275 (2013)Cite this article

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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.

Targeted cancer therapies, directed against defined molecules, are being developed at increasing speed. The identification of cancer subtypes with characteristic driver mutations, important signaling pathways and new drug targets have initiated a multitude of clinical trials. Approval for new drugs first requires efficacy testing in patients with advanced metastatic disease, and the last decade has witnessed some remarkable success stories. For example, targeting metastatic cancers with genetically activated (usually by mutation or amplification) HER2, epidermal growth factor receptor (EGFR) or BRAF has improved survival in subsets of patients with breast, lung or colorectal cancer and patients with melanoma1,2,3,4. Because the benefit in lethal metastatic disease usually lasts a few months only, earlier stages of cancer are subsequently targeted with high expectations that the therapy will work better in the adjuvant setting (systemic treatment of occult disease after surgery).

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

Marina Corral

References

  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

Acknowledgements

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.

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Authors and Affiliations

  1. Bernhard Polzer and Christoph A. Klein are at the Fraunhofer-Institut für Toxikologie und Experimentelle Medizin, Project Group Personalized Tumor Therapy, Regensburg, Germany.,

    Bernhard Polzer & Christoph A Klein

  2. Christoph A. Klein is also at Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany.,

    Christoph A Klein

Authors
  1. Bernhard Polzer
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  2. Christoph A Klein
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Correspondence to Christoph A Klein.

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Polzer, B., Klein, C. Metastasis Awakening: The challenges of targeting minimal residual cancer. Nat Med 19, 274–275 (2013). https://doi.org/10.1038/nm.3121

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