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Therapeutic Implications of TGF-β Pathway in Desmoid Tumor Based on Comprehensive Molecular Profiling and Clinicopathological Properties

Authors :
Kum-Hee Yun
Changhee Park
Hyang Joo Ryu
Chan-Young Ock
Young Han Lee
Wooyeol Baek
Hong In Yoon
Yoon Dae Han
Sang Kyum Kim
JooHee Lee
Seong-Jin Kim
Kyung-Min Yang
Seung Hyun Kim
Hyo Song Kim
Source :
Cancers; Volume 14; Issue 23; Pages: 5975
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

(1) Background: Desmoid tumors have a relatively high local failure rate after primary treatment using surgery and/or radiotherapy. Moreover, desmoid tumors recur at the primary site for many patients. An effective therapeutic strategy for the desmoid tumor is needed to maintain quality of life and prolong survival. (2) Method: First of all, we collected desmoid tumor tissues and investigated the status of protein expression for beta-catenin and alpha-SMA through immunohistochemistry. Then, we performed targeted sequencing and whole RNA sequencing. To compare the data with other cancer types, we used NGS data from sarcoma patients at Yonsei Cancer Center (YCC-sarcoma cohort, n = 48) and The Cancer Genome Atlas (TCGA, n = 9235). Secondly, we established the novel patient-derived preclinical models (n = 2) for the validation of treatment strategy. The same gene alteration of primary tissue was demonstrated. (3) Results: We discovered specific gene sets related to the TGF-β signaling pathway. Moreover, we selected the combination treatment comprising TGF-β inhibitor, vactosertib, and imatinib. In screening for the anti-proliferation effect, the combination treatment of TGF-β inhibitor was more effective for tumor suppression than monotherapy. (4) Conclusion: We found preclinical indications that TGF-β inhibitors could prove useful as a potential treatment for patients with desmoid tumors. Moreover, we could find some examples in clinical trials.

Details

Language :
English
ISSN :
20726694
Database :
OpenAIRE
Journal :
Cancers; Volume 14; Issue 23; Pages: 5975
Accession number :
edsair.doi.dedup.....2be9e47bee41c20c9e2dec9dab243649
Full Text :
https://doi.org/10.3390/cancers14235975