Tumor-stromal interactions in lung cancer: novel candidate targets for therapeutic intervention.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.