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

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.