Department of Lung Development and Remodeling, Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Expert Opin Investig Drugs. 2012 Aug;21(8):1107-22. doi: 10.1517/13543784.2012.693478. Epub 2012 Jun 6.
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.
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.
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.
肺癌是全球癌症死亡的主要原因。尽管新辅助和辅助治疗方案已产生了有希望的结果，但肺癌患者的治疗效果仍不尽人意。最近的数据提供了证据，表明肿瘤-基质环境是致癌作用的主要参与者，而不仅仅是肿瘤的支持性组份。
本文综述了目前对肺癌微环境的理解，以及非小细胞肺癌（NSCLC）中肿瘤与肺部微环境之间复杂的双向相互作用。特别是，本文强调了成纤维细胞、间充质干细胞和髓样细胞的作用，以及这些细胞在肿瘤微环境（TME）中调节的介质和分子途径，这些都有助于肺肿瘤的发生、进展和转移。此外，本文还总结了目前正在进行的临床前和临床试验中的治疗策略。
考虑到对肺肿瘤基质的最新理解进展，通过将细胞毒性策略与靶向 TME 的治疗相结合，可能会有效地阻止肺癌的进展。然而，还需要更多的临床前和临床研究来证明这种治疗非小细胞肺癌的策略的疗效。
