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Review
. 2024 Feb;25(2):161-175.
doi: 10.1007/s11864-024-01177-5. Epub 2024 Jan 25.

Desmoid Tumors: Current Perspective and Treatment

Ankit Mangla  1   2   3 , Nikki Agarwal  4 , Gary Schwartz  5   6   7
Affiliations
Review

Desmoid Tumors: Current Perspective and Treatment

Ankit Mangla et al. Curr Treat Options Oncol. 2024 Feb.

Abstract

Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.

Keywords: Desmoid tumors; Gamma-secretase; Nirogacestat; Sorafenib; Wnt pathway.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Wnt/ β-catenin signaling pathway: Top panel: In the absence of Wnt ligands, β-catenin is destroyed in the cytoplasm by the destruction complex comprising of APC, Axin, CK1, and GSK3β, preventing its translocation to the nucleus. In the absence of intra-nuclear β-catenin, TCF/LEF (family of transcription factors) interacts with Gro and represses transcription. Bottom panel: In the presence of the Wnt ligand, the destruction complex (comprising APC, Axin, CK1, and GSK3β) gets inactivated by binding with LRP5/6. This allows β-catenin to accumulate in the cytoplasm and translocate to the nucleus. In the nucleus, β-catenin dislodges Gro from TCF/LEF and activates the expression of genes. (APC, Adenomatous polyposis coli; CK1, Casein Kinase 1; Gro, Groucho; GSK3β, Glycogen Synthase Kinase 3β; LRP 5/6, Low-Density Lipoprotein receptor-related proteins 5 and 6; TCF/LEF, T-cell/Lymphoid Enhancer Factor; β-cat, β-catenin).
Fig. 2
Fig. 2
Notch Signaling Pathway: Step 1 (occurs in the cytosol): Furin-like protease (Flp) cleaves the immature Notch receptor in the Golgi apparatus. Step 2: Mature notch receptor has an extracellular, transmembrane, and intracellular domain. The extracellular domain interacts with Notch-specific ligands (Jagged-1/2 or Delta-like ligand-1/3/4). Step 3: Mature Notch receptor is cleaved by metalloproteases (ADAM 10/17) and γ-secretase, releasing the Notch-intracellular domain. Step 4: Notch-intracellular domain translocates to the nucleus and forms a complex with transcription factors recombination signal binding protein for immunoglobulin kappa J region (RBP-J) and Mastermind-like proteins (MAML), which leads to transcription of proteins. (Flp, Furin-like protein; GSI, Gamma-Secretase Inhibitor; HES, Hairy Enhancer of Split; MAML, Mastermind-like proteins; NEMD, Notch-Extracellular Domain; NICD, Notch-Intracellular Domain; NTMD, Notch-Transmembrane Domain; RBP-J, Recombination Signal Binding Protein for Immunoglobulin Kappa J region).
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References

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance
    1. Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO classification of soft tissue tumours: news and perspectives. Pathologica. 2021;113(2):70–84. doi: 10.32074/1591-951X-213. - DOI - PMC - PubMed
    1. Fong Y, Rosen PP, Brennan MF. Multifocal desmoids. Surgery. 1993;114(5):902–906. - PubMed
    1. Bekers EM, van Broekhoven DLM, van Dalen T, et al. Multifocal occurrence of extra-abdominal desmoid type fibromatosis - a rare manifestation. A clinicopathological study of 6 sporadic cases and 1 hereditary case. Ann Diagn Pathol. 2018;35:38–41. doi: 10.1016/j.anndiagpath.2018.04.001. - DOI - PubMed
    1. Bonvalot S, Desai A, Coppola S, et al. The treatment of desmoid tumors: a stepwise clinical approach. Ann Oncol. 2012;23(Suppl 10):x158–166. doi: 10.1093/annonc/mds298. - DOI - PubMed
    1. Alman B, Attia S, Baumgarten C, et al. The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96–107. doi: 10.1016/j.ejca.2019.11.013. - DOI - PubMed

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