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

Research output: Chapter in Book/Report/Conference proceedingChapter

45 Scopus citations

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 infl ammation, 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. Infl ammation 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 effi cacy 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.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York
Pages75-110
Number of pages36
DOIs
StatePublished - Oct 1 2016

Publication series

NameAdvances in Experimental Medicine and Biology
Volume890
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Angiogenesis
  • Bone marrow
  • Endothelial cells
  • Hypoxia
  • Immune cells
  • Immunotherapy
  • Infl ammation
  • Lung cancer
  • Microenvironment
  • Radiation
  • Resistance
  • Therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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