The Microenvironment of Lung Cancer and Therapeutic Implications

  • Vivek Mittal
  • Tina El Rayes
  • Navneet Narula
  • Timothy E. McGraw
  • Nasser K Altorki
  • Mary Helen Barcellos-Hoff
Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 890)

Abstract

The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetically stable intratumoral stromal cells result in an “activated/reprogramed” stroma that promotes carcinogenesis by contributing to inflammation, immune suppression, therapeutic resistance, and generating premetastatic niches that support the initiation and establishment of distant metastasis. The lungs present a unique milieu in which tumors progress in collusion with the TME, as evidenced by regions of aberrant angiogenesis, acidosis and hypoxia. Inflammation plays an important role in the pathogenesis of lung cancer, and pulmonary disorders in lung cancer patients such as chronic obstructive pulmonary disease (COPD) and emphysema, constitute comorbid conditions and are independent risk factors for lung cancer. The TME also contributes to immune suppression, induces epithelial-to-mesenchymal transition (EMT) and diminishes efficacy of chemotherapies. Thus, the TME has begun to emerge as the “Achilles heel” of the disease, and constitutes an attractive target for anti-cancer therapy. Drugs targeting the components of the TME are making their way into clinical trials. Here, we will focus on recent advances and emerging concepts regarding the intriguing role of the TME in lung cancer progression, and discuss future directions in the context of novel diagnostic and therapeutic opportunities.

Keywords

Microenvironment Lung cancer Inflammation Immune cells Angiogenesis Endothelial cells Bone marrow Hypoxia Therapy Immunotherapy Radiation Resistance 
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Notes

Acknowledgement

We thank Sharell Lee for reading the manuscript.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Vivek Mittal
    • 2
    • 3
    • 1
  • Tina El Rayes
    • 2
    • 3
    • 1
    • 4
  • Navneet Narula
    • 5
  • Timothy E. McGraw
    • 2
    • 3
    • 6
  • Nasser K Altorki
    • 2
    • 3
  • Mary Helen Barcellos-Hoff
    • 7
  1. 1.Department of Cell and Developmental BiologyWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Department of Cardiothoracic SurgeryWeill Medical College of Cornell UniversityNew YorkUSA
  3. 3.Neuberger Berman Lung Cancer Research CenterWeill Medical College of Cornell UniversityNew YorkUSA
  4. 4.Weill Cornell Graduate School of Medical SciencesWeill Medical College of Cornell UniversityNew YorkUSA
  5. 5.Department of PathologyWeill Medical College of Cornell UniversityNew YorkUSA
  6. 6.Department of BiochemistryWeill Medical College of Cornell UniversityNew YorkUSA
  7. 7.Department of Radiation OncologyNew York University School of MedicineNew YorkUSA

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