# TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer

## TL;DR

This paper shows how TGF-β signaling connects lung fibrosis and lung cancer, suggesting shared disease mechanisms and new treatment strategies.

## Contribution

The paper introduces a unifying framework where TGF-β signaling acts as a pathological continuum linking idiopathic pulmonary fibrosis and lung cancer.

## Key findings

- Persistent TGF-β signaling affects epithelial cells, fibroblasts, and immune cells in both diseases.
- The timing and intensity of TGF-β activation determine whether it leads to fibrosis or cancer.
- Combining TGF-β modulation with immunotherapy or anti-fibrotic agents is a promising treatment approach.

## Abstract

What are the main findings?
Persistent and dysregulated TGF-β signaling constitutes a shared pathogenic axis linking idiopathic pulmonary fibrosis and lung cancer through coordinated effects on epithelial cells, fibroblasts, and the immune microenvironment.The temporal intensity and cellular context of TGF-β activation critically determine its transition from physiological repair to pathological fibrosis, immune suppression, and tumor progression.

Persistent and dysregulated TGF-β signaling constitutes a shared pathogenic axis linking idiopathic pulmonary fibrosis and lung cancer through coordinated effects on epithelial cells, fibroblasts, and the immune microenvironment.

The temporal intensity and cellular context of TGF-β activation critically determine its transition from physiological repair to pathological fibrosis, immune suppression, and tumor progression.

What are the implications of the main findings?
Therapeutic targeting of TGF-β signaling requires precision strategies that distinguish pathological activation from its essential physiological functions to avoid adverse effects.Context-specific and combinatorial approaches, particularly integrating TGF-β modulation with immunotherapy or anti-fibrotic agents, represent promising directions for future clinical translation.

Therapeutic targeting of TGF-β signaling requires precision strategies that distinguish pathological activation from its essential physiological functions to avoid adverse effects.

Context-specific and combinatorial approaches, particularly integrating TGF-β modulation with immunotherapy or anti-fibrotic agents, represent promising directions for future clinical translation.

Transforming growth factor-β (TGF-β) signaling plays a central role in lung tissue homeostasis, coordinating epithelial repair, immune resolution, and stromal remodeling following injury. However, persistent or dysregulated TGF-β activation is a hallmark of both idiopathic pulmonary fibrosis (IPF) and lung cancer, two devastating pulmonary diseases that are traditionally studied as distinct entities. Emerging evidence suggests that this dichotomous view may obscure shared pathogenic mechanisms driven by aberrant TGF-β signaling dynamics. In this review, we synthesize experimental, translational, and clinical findings to propose a unifying framework in which IPF and lung cancer represent endpoints along a shared TGF-β–driven pathological continuum. We highlight how the duration and intensity of TGF-β signaling determine divergent cellular outcomes across epithelial cells, fibroblasts, and immune compartments—ranging from physiological wound repair to irreversible fibrotic remodeling and the establishment of a pro-tumorigenic niche. Particular emphasis is placed on the temporal transition from acute injury responses to chronic signaling states that promote epithelial plasticity, fibroblast fixation, immune suppression, and genomic instability. By integrating fibrosis and tumorigenesis into a single pathophysiological model, this review reframes TGF-β signaling as a time-dependent disease modifier rather than a disease-specific factor. This perspective provides a conceptual basis for therapeutic strategies targeting TGF-β signaling windows to intercept disease progression before irreversible fibrosis or malignant transformation occurs.