Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, NY, USA.
Neuberger Berman Foundation Lung Cancer Research Center, Weill Cornell Medicine, New York, NY, USA.
Nat Rev Cancer. 2019 Jan;19(1):9-31. doi: 10.1038/s41568-018-0081-9.
Lung cancer is a major global health problem, as it is the leading cause of cancer-related deaths worldwide. Major advances in the identification of key mutational alterations have led to the development of molecularly targeted therapies, whose efficacy has been limited by emergence of resistance mechanisms. US Food and Drug Administration (FDA)-approved therapies targeting angiogenesis and more recently immune checkpoints have reinvigorated enthusiasm in elucidating the prognostic and pathophysiological roles of the tumour microenvironment in lung cancer. In this Review, we highlight recent advances and emerging concepts for how the tumour-reprogrammed lung microenvironment promotes both primary lung tumours and lung metastasis from extrapulmonary neoplasms by contributing to inflammation, angiogenesis, immune modulation and response to therapies. We also discuss the potential of understanding tumour microenvironmental processes to identify biomarkers of clinical utility and to develop novel targeted therapies against lung cancer.
肺癌是一个全球性的重大健康问题,因为它是全球癌症相关死亡的主要原因。在鉴定关键突变改变方面的重大进展导致了分子靶向治疗的发展,但其疗效受到耐药机制的限制。美国食品和药物管理局(FDA)批准的针对血管生成的治疗方法,以及最近的免疫检查点治疗方法,重新激发了人们对阐明肺癌肿瘤微环境的预后和病理生理作用的热情。在这篇综述中,我们强调了最近的进展和新出现的概念,即肿瘤重编程的肺微环境如何通过促进炎症、血管生成、免疫调节和对治疗的反应,促进原发性肺肿瘤和来自肺外肿瘤的肺转移。我们还讨论了理解肿瘤微环境过程的潜力,以确定具有临床应用价值的生物标志物,并开发针对肺癌的新型靶向治疗方法。