Zullo Lodovica, Filippiadis Dimitris, Hendriks Lizza E L, Portik Daniel, Spicer Jonathan D, Wistuba Ignacio I, Besse Benjamin
Cancer Medicine Department, Gustave Roussy, Villejuif, France.
Department of Experimental Medicine, University of Genova, Genova, Italy.
Nat Rev Dis Primers. 2025 Aug 21;11(1):60. doi: 10.1038/s41572-025-00642-1.
Up to 50% of patients with metastatic cancer develop lung metastases during their disease course. Lung metastases are linked to poor prognosis across various cancer types and might impair the quality of life of patients, causing dyspnoea, cough, haemoptysis and pain, potentially diminishing physical, functional and emotional well-being. Lung metastases arise from a complex interplay of tumour-secreted factors such as VEGF, TGFβ and CCL2, which drive vascular remodelling, immune cell recruitment and extracellular matrix reprogramming. Additionally, tumour-derived exosomes and microparticles contribute to organotropism and immunosuppression by altering the lung microenvironment. The ensemble of these modifications creates a pre-metastatic niche conducive to tumour cell colonization and outgrowth. Lung metastases are primarily diagnosed through imaging; histological confirmation is sometimes required to distinguish them from primary lung cancer. The size and number of lung metastases, timing of primary cancer treatment, histology, and the patient's clinical condition are all considered to determine the most appropriate treatment. When a locoregional approach is not possible, histology-based, molecular-driven systemic therapy is the choice. No systemic treatment is currently available specifically for lung metastases. Advances in understanding the distinct stages of pre-metastatic niche formation and lung metastasis outgrowth might lead to the development of prevention strategies and tailored treatments.
高达50%的转移性癌症患者在病程中会发生肺转移。肺转移与多种癌症类型的预后不良相关,可能会损害患者的生活质量,导致呼吸困难、咳嗽、咯血和疼痛,可能会降低身体、功能和情感幸福感。肺转移源于肿瘤分泌因子(如血管内皮生长因子、转化生长因子β和趋化因子配体2)的复杂相互作用,这些因子驱动血管重塑、免疫细胞募集和细胞外基质重编程。此外,肿瘤衍生的外泌体和微粒通过改变肺微环境促进器官趋向性和免疫抑制。这些改变共同形成了一个有利于肿瘤细胞定植和生长的前转移微环境。肺转移主要通过影像学诊断;有时需要组织学确认以将它们与原发性肺癌区分开来。在确定最合适的治疗方案时,会考虑肺转移灶的大小和数量、原发性癌症的治疗时机、组织学以及患者的临床状况。当无法采用局部治疗方法时,基于组织学和分子驱动的全身治疗是首选。目前尚无专门针对肺转移的全身治疗方法。对前转移微环境形成和肺转移生长不同阶段的深入了解可能会带来预防策略和定制治疗方法的发展。