Hallmarks of lung cancer driven by inhalable particulate matter: From cell-intrinsic oncogenic traits to microenvironment remodeling

Inhalable particulate matter (PM) has emerged as a critical yet underappreciated carcinogenic factor in lung cancer, especially affecting non-smokers and populations residing in heavily polluted regions. Epidemiological research has confirmed the link between PM exposure and lung cancer risk, but the underlying biological pathways and clinical relevance are still not well understood. Here, we provide a comprehensive synthesis of current advances in PM-associated lung carcinogenesis, from population-level risk patterns to molecular pathogenesis and translational strategies. We outline the epidemiological burden and unique clinical features of PM-related lung cancer. We then propose a “Hallmarks of PM-associated lung cancer” framework, summarizing twelve features of how lung cancer evolves under PM exposure.

This involves a complex interplay of cell-intrinsic oncogenic traits induced by PM (genetic alterations, epigenetic reprogramming, metabolic remodeling, stemness) and microenvironment reshaped by PM (inflammatory responses, immune suppression, angiogenesis, and pre-metastatic niche formation). Moreover, we critically examine the technical challenges in mechanistic studies and propose future solutions. Finally, we highlight urgent opportunities for integrating PM exposure into lung cancer screening, risk stratification, and prevention policies. This review offers a comprehensive framework for strategies to downsize the impact of air pollution on global lung health.