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The Microenvironment of Lung Cancer and Therapeutic Implications

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Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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Acknowledgement

We thank Sharell Lee for reading the manuscript.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Vivek Mittal & Tina El Rayes

  2. Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Vivek Mittal, Tina El Rayes, Timothy E. McGraw & Nasser K Altorki

  3. Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Vivek Mittal, Tina El Rayes, Timothy E. McGraw & Nasser K Altorki

  4. Weill Cornell Graduate School of Medical Sciences, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Tina El Rayes

  5. Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Navneet Narula

  6. Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA

    Timothy E. McGraw

  7. Department of Radiation Oncology, New York University School of Medicine, 566 First Avenue, New York, NY, 10016, USA

    Mary Helen Barcellos-Hoff

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  1. Vivek Mittal
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  2. Tina El Rayes
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  3. Navneet Narula
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  4. Timothy E. McGraw
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  5. Nasser K Altorki
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  6. Mary Helen Barcellos-Hoff
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Corresponding authors

Correspondence to Vivek Mittal or Mary Helen Barcellos-Hoff .

Editor information

Editors and Affiliations

  1. Wayne State University, Karmanos Cancer Institute, Detroit, Michigan, USA

    Aamir Ahmad

  2. Karamanos Cancer Institute, Wayne State University, Detroit, Michigan, USA

    Shirish M. Gadgeel

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Mittal, V., El Rayes, T., Narula, N., McGraw, T.E., Altorki, N.K., Barcellos-Hoff, M.H. (2016). The Microenvironment of Lung Cancer and Therapeutic Implications. In: Ahmad, A., Gadgeel, S. (eds) Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. Advances in Experimental Medicine and Biology, vol 890. Springer, Cham. https://doi.org/10.1007/978-3-319-24932-2_5

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