Molecular Mechanisms Underlying Progression and Spontaneous Regression in Desmoid Tumors
- 1Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
Abstract
Desmoid-type fibromatosis, also known as desmoid tumor (DT), is a rare and locally aggressive soft tissue neoplasm driven by constitutive activation of the Wnt/β-catenin signaling pathway, most commonly through CTNNB1 or APC alterations. While some tumors progress and cause substantial morbidity, approximately 25–38% undergo spontaneous regression during active surveillance, which is currently recommended as the first-line management strategy. Although advances in next-generation sequencing and transcriptomic profiling have elucidated the molecular drivers of tumor progression, the molecular mechanisms underlying spontaneous regression remain poorly understood. This review summarizes current knowledge of the molecular pathogenesis of DT and proposed mechanisms of spontaneous regression, including attenuation of Wnt/β-catenin signaling, hormonal modulation, alterations in the immune microenvironment, and crosstalk between Wnt signaling and other pathways such as Notch, PDGFR/c-Abl/HIF1α, and TGF-β. Based on the current knowledge of the molecular mechanisms in DT, spontaneous regression appears to reflect a multifactorial transition from an active proliferative state toward a quiescent, fibrotic phenotype rather than a single molecular event. Further studies integrating single-cell and spatial transcriptomics with immune profiling are warranted to identify therapeutic targets and stratify patients for active surveillance versus active treatment.
Related
- Advances in the molecular mechanisms underlying autogenous arteriovenous fistula maturation failure
- Molecular mechanisms underlying phenotypic overlap and AI-misclassification in rare bone diseases: Insights from SHOX-related signaling pathways in endochondral ossification
- Study on the Active Constituents and Underlying Mechanisms of Renshen Yangying Decoction Against Angina Pectoris Based on Integrated Serum Pharmacochemistry, Network Pharmacology, Molecular Docking, and Experimental Validation
- Prometheus’s Fire, Part I: The Flight of Icarus—Molecular Mechanisms Underlying Adipose Tissue Dysfunction in Obesity: From Adaptive Hyperplasia to Pathological Hypertrophy
- Exosomes-mediated molecular mechanisms underlying the transformation of ovarian tissue into a functional placental analogue in black rockfish (Sebastes schlegelii)
BibTeX
@article{miwa2026molecular,
title = {{Molecular Mechanisms Underlying Progression and Spontaneous Regression in Desmoid Tumors}},
author = {Shinji Miwa and Katsuhiro Hayashi and Takashi Higuchi and Hirotaka Yonezawa and Sei Morinaga and Yohei Asano and Satoru Demura},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198887},
url = {https://www.mdpi.com/1422-0067/27/19/8887},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular Mechanisms Underlying Progression and Spontaneous Regression in Desmoid Tumors
AU - Shinji Miwa
AU - Katsuhiro Hayashi
AU - Takashi Higuchi
AU - Hirotaka Yonezawa
AU - Sei Morinaga
AU - Yohei Asano
AU - Satoru Demura
PY - 2026
DA - 2026/10/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198887
UR - https://www.mdpi.com/1422-0067/27/19/8887
AB - Desmoid-type fibromatosis, also known as desmoid tumor (DT), is a rare and locally aggressive soft tissue neoplasm driven by constitutive activation of the Wnt/β-catenin signaling pathway, most commonly through CTNNB1 or APC alterations. While some tumors progress and cause substantial morbidity, approximately 25–38% undergo spontaneous regression during active surveillance, which is currently recommended as the first-line management strategy. Although advances in next-generation sequencing and transcriptomic profiling have elucidated the molecular drivers of tumor progression, the molecular mechanisms underlying spontaneous regression remain poorly understood. This review summarizes current knowledge of the molecular pathogenesis of DT and proposed mechanisms of spontaneous regression, including attenuation of Wnt/β-catenin signaling, hormonal modulation, alterations in the immune microenvironment, and crosstalk between Wnt signaling and other pathways such as Notch, PDGFR/c-Abl/HIF1α, and TGF-β. Based on the current knowledge of the molecular mechanisms in DT, spontaneous regression appears to reflect a multifactorial transition from an active proliferative state toward a quiescent, fibrotic phenotype rather than a single molecular event. Further studies integrating single-cell and spatial transcriptomics with immune profiling are warranted to identify therapeutic targets and stratify patients for active surveillance versus active treatment.
SN - 1422-0067
ER -