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.

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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

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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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Correspondence to Christoph A Klein.

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The authors declare no competing financial interests.

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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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