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Regulation of Tumor Progression and Metastasis by Bone Marrow-Derived Microenvironments

Chapter

Abstract

Activating mutations in driver oncogenes and loss-of-function mutations in tumor suppressor genes contribute to tumor progression and metastasis. Accordingly, therapies targeting key tumor cell-intrinsic signaling pathways are being used in clinical trials, and some have met FDA approval. However, these treatments benefit only a small proportion of patients harboring key driver mutations, and acquired resistance to these therapies presents a major impediment to effective treatment. More recently, the contribution of the tumor microenvironment (TME) has been an area of active investigation and has begun to provide critical insights into carcinogenesis. The host stromal cells in the TME coevolve with tumors and contribute to carcinogenesis in several ways. Among the host cells, bone marrow (BM)-derived cells constitute a significant fraction and directly contribute to proliferation, invasion, intravasation, extravasation, and outgrowth at the metastatic site. While the tumor-reprogrammed BM cells constitute attractive targets for anticancer therapy, recent studies have also begun to unravel their role as prognostic and predictive molecular markers of the disease.

Keywords

Metastasis Tumor microenvironment Bone marrow  •  Anti-cancer therapy Pre-metastatic niche Tumor progression Bone marrow-derived cells 

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Tina El Rayes
    • 1
  • Dingcheng Gao
    • 2
    • 3
    • 4
  • Nasser K. Altorki
    • 3
    • 4
  • Thomas R. Cox
    • 5
  • Janine  T.  Erler
    • 5
  • Vivek Mittal
    • 2
    • 3
    • 4
  1. 1.Department of ImmunologySloan Kettering InstituteNew YorkUSA
  2. 2.Department of Cell and Developmental BiologyWeill Cornell MedicineNew YorkUSA
  3. 3.Department of Cardiothoracic SurgeryWeill Cornell MedicineNew YorkUSA
  4. 4.Neuberger Berman Foundation Lung Cancer CenterWeill Cornell MedicineNew YorkUSA
  5. 5.Biotech Research and Innovation Centre (BRIC)University of Copenhagen (UCPH)CopenhagenDenmark

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