# Reprogrammed Fibrotic Niche Fuels Lung Cancer Initiation and Reciprocal Remodeling

## TL;DR

This paper explores how lung fibrosis and lung cancer influence each other through changes in the lung's environment, offering new treatment strategies.

## Contribution

The paper introduces novel therapeutic strategies targeting the fibrotic microenvironment in the context of PF-LC comorbidity.

## Key findings

- Chronic inflammation and matrix stiffness in fibrotic niches promote lung cancer initiation.
- Bidirectional interactions between lung cancer and fibrotic processes drive disease progression.
- Targeting the fibrotic microenvironment presents a potential clinical strategy for treating PF-LC comorbidity.

## Abstract

Pulmonary Fibrosis (PF), an end-stage manifestation of interstitial lung diseases, is associated with largely unfavorable prognoses. Lung cancer (LC), a leading cause of nationally cancer-related mortality with progressively increasing incidence, exhibits pathological interconnections with PF. The chronic remodeling of the pulmonary microenvironment—including cellular components, extracellular matrix (ECM), inflammatory cytokine networks, and metabolic reprogramming—represents the core pathogenic mechanism underlying PF-LC comorbidity. This review systematically elaborates how the fibrotic microenvironment promotes malignant transformation of lung cancer via chronic inflammation, increased matrix stiffness, immunosuppressive regulation, and epigenetic modulation. Furthermore, we investigate the bidirectional crosstalk by which LC progression reciprocally modulates fibrotic processes. Finally, we integrate current clinical challenges and propose novel therapeutic strategies targeting the fibrotic microenvironment to address this lethal pathophysiological synergy.