title: The Microenvironment of Lung Cancer and Therapeutic Implications.
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.
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA. vim2010@med.cornell.edu.|Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA. vim2010@med.cornell.edu.|Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA. vim2010@med.cornell.edu.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mittal
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Weill Cornell Graduate School of Medical Sciences, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: El Rayes
authors.affiliation: Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Navneet
authors.initials: N
authors.lastname: Narula
authors.affiliation: Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: McGraw
authors.affiliation: Department of Cardiothoracic Surgery, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.|Neuberger Berman Lung Cancer Research Center, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Altorki
authors.affiliation: Department of Radiation Oncology, New York University School of Medicine, 566 First Avenue, New York, NY, 10016, USA. MHBarcellos-Hoff@nyumc.org.
authors.forename: Mary Helen
authors.initials: MH
authors.lastname: Barcellos-Hoff
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011656:Pulmonary Emphysema / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
keywords: Angiogenesis; Bone marrow; Endothelial cells; Hypoxia; Immune cells; Immunotherapy; Inflammation; Lung cancer; Microenvironment; Radiation; Resistance; Therapy