Tumor-stromal interactions in lung cancer: novel candidate targets for therapeutic intervention.
BACKGROUND
Lung cancer is the leading cause of cancer deaths worldwide. Although standard treatment regimens have produced promising results with neoadjuvant and adjuvant strategies, outcomes for patients with lung cancer are still considered disappointing. Recent data provide evidence that the tumor-stromal environment is a leading player in carcinogenesis, not just a supporting tumor compartment.


METHODS
This article reviews the current understanding of the lung cancer microenvironment and the complex bidirectional interplay between the tumor and lung microenvironment in non-small cell lung cancer (NSCLC). In particular, this review emphasizes the role of fibroblasts, mesenchymal stem cells and myeloid cells as well as mediators and molecular pathways regulated by these cells within the tumor microenvironment (TME) that contribute to lung tumor initiation, progression and metastasis. In addition, this review also summarizes the therapeutic strategies currently being applied in preclinical and clinical trials.


CONCLUSIONS
Considering the recent advances in understanding lung tumor stroma, lung cancer progression could be effectively hampered by combining cytotoxic strategies with therapies that target the TME. However, more preclinical and clinical research is needed to prove the efficacy of this strategy for treating NSCLC.
Department of Lung Development and Remodeling, Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Nefertiti
N
El-Nikhely
Leyre
L
Larzabal
Werner
W
Seeger
Alfonso
A
Calvo
Rajkumar
R
Savai
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D058990:Molecular Targeted Therapy; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents