Aberrant fibrotic phenotypes of tumor-associated fibroblasts in lung cancer: translational opportunities
Jordi Alcaraz
Universitat de Barcelona
Lung cancer is the leading cause of cancer-related death in both women and men in Spain and worldwide. Tumor-associated fibroblasts (TAFs) are the most abundant cell type within the tumor microenvironment and are key contributors to all steps of tumor-progression and therapy resistance. Most TAFs exhibit a fibrotic/myofibroblast-like phenotype in lung cancer. Yet, our work has revealed that fibrosis is regulated through different processes according to the histologic subtype in non-small cell lung cancer (NSCLC), and that aberrant TGF-b1/SMAD3 signaling is essential for this regulation. In this seminar we will also describe additional phenotypic alterations of TAFs for the most common histologic subtypes of NSCLC, including senescence, altered mechanobiology angiogenesis and immunosuppression. Finally, we will show how TAF-associated molecular alterations may provide new diagnostic/prognostic biomarkers and identify novel therapeutic approaches to improve the clinical management of NSCLC.