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The neurokinin-1 receptor is a target in pediatric rhabdoid tumors.
Curr. Oncol. 29, 94-110 (2022)
Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Apoptosis ; Cancer ; Nk-1 Receptor ; Nk-1 Receptor Antagonist ; Rhabdoid Tumor ; Substance P; Atypical Teratoid/rhabdoid Tumors; Substance-p; Childhood Neuroblastoma; Nk-1 Receptor; Hepatoblastoma; Antagonists; Biology; Cells; Smarcb1/ini1; Chemotherapy
ISSN (print) / ISBN
1198-0052
e-ISSN
1718-7729
Journal
Current Oncology
Quellenangaben
Volume: 29,
Issue: 1,
Pages: 94-110
Publisher
MDPI
Publishing Place
St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants
Promotionsstudium Förderung für Forschung und Lehre" program from the University of Mu-nich, LMU