# Progression and Metastasis of Lung Cancer: Clinical Features, Molecular Mechanisms, and Clinical Managements

## TL;DR

This paper reviews how lung cancer spreads to the liver, bone, and brain, focusing on clinical features, molecular mechanisms, and treatment strategies to improve outcomes.

## Contribution

The paper provides a systematic synthesis of metastatic mechanisms and treatment approaches for three critical sites of lung cancer metastasis.

## Key findings

- Liver metastases benefit from immune checkpoint inhibitors and early detection via liquid biopsies.
- Bone metastases require biomarker-driven therapies and multimodal pain management.
- Brain metastases demand strategies to overcome the blood–brain barrier and address tumor heterogeneity.

## Abstract

Lung cancer remains a leading cause of cancer‐related mortality worldwide, with metastasis leading to a poor prognosis. While advances in primary tumor management have improved survival, disease dissemination to distant organs, particularly the liver, bone, and brain, represents an unresolved therapeutic challenge. Metastasis is governed by complex interactions between tumor cells and the microenvironment, including immune evasion, angiogenesis, and organotropism. Current therapies often fail to address site‐specific molecular vulnerabilities or overcome physiological barriers such as the blood–brain barrier (BBB). A systematic review integrating clinical and mechanistic insights is urgently needed to guide translational efforts. This review synthesizes evidence on lung cancer metastases to three critical sites: liver metastases, where immunosuppressive niches and delayed diagnosis limit outcomes, and we emphasize the role of immune checkpoint inhibitors and liquid biopsies; bone metastases, characterized by osteolytic/osteoblastic lesions, which require biomarker‐driven therapies and multimodal pain management; and brain metastases, where BBB penetration and heterogeneity demand tailored approaches. By dissecting organ‐specific mechanisms, including circulating tumor cells, premetastatic niche formation, and metabolic reprogramming, this work highlights actionable targets for precision medicine. This review advocates for patient stratification and combination therapies to improve survival, offering a roadmap for future research on metastatic lung cancer.

Lung cancer represents a significant global health threat. Despite progress in treatment, metastasis continues to present a major clinical challenge. This article reviews the metastases of lung cancer to the liver, bone, and brain, focusing on clinical symptoms, molecular mechanisms, and treatment strategies. Liver metastases from lung cancer underscore the need for early detection, rigorous monitoring, and prompt intervention. Enhancing systemic anti‐cancer immunity and reducing immunosuppression may improve therapeutic outcomes in these cases. Bone metastases highlight the critical role of biomarkers and the necessity of personalized and multimodal treatment approaches to enhance patient outcomes. For brain metastases, seen in both non‐small cell lung cancer and small cell lung cancer, a multidisciplinary treatment approach is essential. Future research must address immune evasion and strategies for overcoming the blood–brain barrier. Overall, this paper emphasizes the importance of understanding the pathways of metastasis to develop more effective treatments. It advocates for personalized treatment strategies targeting metastases at different sites.