Congenital pulmonary airway malformation: molecular mechanisms and exploration of candidate therapeutic pathways
Abstract
Congenital pulmonary airway malformation (CPAM), formerly termed congenital cystic adenomatoid malformation, is a heterogeneous developmental lung disorder characterized by abnormal cystic or adenomatous structures. Its pathogenesis remains incompletely understood and may involve disturbed lung branching morphogenesis, altered epithelial differentiation, imbalanced cell proliferation and apoptosis, focal somatic mutations, and abnormal epithelial–mesenchymal interactions. This comprehensive narrative review discusses molecular findings relevant to CPAM, including Hoxb-5, SOX2, NKX2.1/TTF-1, FGF10, WNT/BMP, EGFR, RAS–MAPK, PI3K–AKT–mTOR, ACSL5/WNT2B, FABP7, and TGF-β signaling. We distinguish evidence obtained directly from human CPAM tissue—including expression studies and somatic mutation analyses—from findings extrapolated from normal lung development, animal models, and other pulmonary disorders. Recent morphological, immunohistochemical, molecular, and single-cell studies support substantial histological and molecular heterogeneity, while the relationship between specific histological subtypes and precise developmental windows remains provisional. Chromosomal microarray analysis and sequencing may help identify selected genomic abnormalities, but most candidate pathways have not yet been validated as causal or clinically actionable targets. We summarize key evidence gaps and outline priorities for tissue-resolved profiling, functional validation in organoid and developmental models, and cautious assessment of therapeutic feasibility and safety. This review aims to provide a critical framework for interpreting current CPAM molecular evidence and guiding future translational research.
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BibTeX
@article{chang2026congenital,
title = {{Congenital pulmonary airway malformation: molecular mechanisms and exploration of candidate therapeutic pathways}},
author = {Ruitong Chang and Yongming Ma and Baowei Meng and Xiaogang Yang and Zhiqiang Wu and Zijiang Zhu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1970157},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1970157},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Congenital pulmonary airway malformation: molecular mechanisms and exploration of candidate therapeutic pathways
AU - Ruitong Chang
AU - Yongming Ma
AU - Baowei Meng
AU - Xiaogang Yang
AU - Zhiqiang Wu
AU - Zijiang Zhu
PY - 2026
DA - 2026/11/03
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1970157
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1970157
AB - Congenital pulmonary airway malformation (CPAM), formerly termed congenital cystic adenomatoid malformation, is a heterogeneous developmental lung disorder characterized by abnormal cystic or adenomatous structures. Its pathogenesis remains incompletely understood and may involve disturbed lung branching morphogenesis, altered epithelial differentiation, imbalanced cell proliferation and apoptosis, focal somatic mutations, and abnormal epithelial–mesenchymal interactions. This comprehensive narrative review discusses molecular findings relevant to CPAM, including Hoxb-5, SOX2, NKX2.1/TTF-1, FGF10, WNT/BMP, EGFR, RAS–MAPK, PI3K–AKT–mTOR, ACSL5/WNT2B, FABP7, and TGF-β signaling. We distinguish evidence obtained directly from human CPAM tissue—including expression studies and somatic mutation analyses—from findings extrapolated from normal lung development, animal models, and other pulmonary disorders. Recent morphological, immunohistochemical, molecular, and single-cell studies support substantial histological and molecular heterogeneity, while the relationship between specific histological subtypes and precise developmental windows remains provisional. Chromosomal microarray analysis and sequencing may help identify selected genomic abnormalities, but most candidate pathways have not yet been validated as causal or clinically actionable targets. We summarize key evidence gaps and outline priorities for tissue-resolved profiling, functional validation in organoid and developmental models, and cautious assessment of therapeutic feasibility and safety. This review aims to provide a critical framework for interpreting current CPAM molecular evidence and guiding future translational research.
SN - 1663-9812
ER -