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Chemotherapy-induced metastasis: mechanisms and translational opportunities

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Abstract

Tumors often overcome the cytotoxic effects of chemotherapy through either acquired or environment-mediated drug resistance. In addition, signals from the microenvironment obfuscate the beneficial effects of chemotherapy and may facilitate progression and metastatic dissemination. Seminal mediators in chemotherapy-induced metastasis appear to be a wide range of hematopoietic, mesenchymal and immune progenitor cells, originating from the bone marrow. The actual purpose of these cells is to orchestrate the repair response to the cytotoxic damage of chemotherapy. However, these repair responses are exploited by tumor cells at every step of the metastatic cascade, ranging from tumor cell invasion, intravasation and hematogenous dissemination to extravasation and effective colonization at the metastatic site. A better understanding of the mechanistic underpinnings of chemotherapy-induced metastasis will allow us to better predict which patients are more likely to exhibit pro-metastatic responses to chemotherapy and will help develop new therapeutic strategies to neutralize chemotherapy-driven prometastatic changes.

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Funding

This article is supported by grants from the NIH (CA100324, CA150344 and CA216248), the SIG 1S10OD019961-01, the Gruss-Lipper Biophotonics center and its associated Integrative Imaging Program at the Albert Einstein College of Medicine.

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GSK, JSC and MHO conceived the idea and wrote the manuscript.

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Correspondence to George S. Karagiannis, John S. Condeelis or Maja H. Oktay.

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MHO and JSC are inventors on a patent application (#96700/2505) submitted by the Albert Einstein College of Medicine that covers methods detecting and reducing chemotherapy-induced prometastatic changes in breast tumors. GSK declares no competing interests.

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Karagiannis, G.S., Condeelis, J.S. & Oktay, M.H. Chemotherapy-induced metastasis: mechanisms and translational opportunities. Clin Exp Metastasis 35, 269–284 (2018). https://doi.org/10.1007/s10585-017-9870-x

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  • DOI: https://doi.org/10.1007/s10585-017-9870-x

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