"Tamoxifen for residual NF-PitNETs: a Proof-of-Concept study integrating receptor profiling, pilot trial, and target pathway analysis"

Haydar Ali Tajuddin, Amalina and Rullah, Kamal and Isa, Nur Firdaus and Mohd Nasir, Mohd Hamzah and Uddin, Md Nazim and Omar, Ahmad Marzuki (2025) "Tamoxifen for residual NF-PitNETs: a Proof-of-Concept study integrating receptor profiling, pilot trial, and target pathway analysis". Endocrine. pp. 1-14. E-ISSN 1559-0100

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Abstract

Background Non-functioning neuroendocrine pituitary neuroendocrine tumors (NF-PitNETs) pose a therapeutic challenge due to their hormonal inactivity, mass effects and limited medical treatment options for residual or recurrent disease. There is increasing evidence that the oestrogen receptor (ER) is involved in the pathogenesis of these tumours. In this study, the potential therapeutic role of tamoxifen, a selective ER modulator, was investigated. Methods Fifty NF-PitNET samples were analysed for ERα and ERβ expression by immunohistochemistry. A randomised, open-label clinical trial was conducted in 20 patients with postoperative residual tumours comparing tamoxifen treatment (n = 10) with observation (n = 10), with MRI volume analysis performed at baseline and after six months. In parallel, tamoxifen targets were predicted with SwissTargetPrediction and analysed with enrichment tools (DAVID, STRING, Cytoscape). Results ERβ expression was present in 68% of tumours, while ERα was detected in 18%. In the tamoxifen group, the tumour shrank in 40% of patients and the disease remained stable in 60%. In contrast, tumour progression occurred in 20% of patients in the observation group (p = 0.043). The computational analysis revealed 109 predicted tamoxifen targets that were significantly enriched in neuroactive ligand–receptor interactions, calcium signalling and cAMP pathways. Gene ontology terms indicated involvement in G protein-coupled receptor activities and synaptic signalling pathways, with key nodes being AKT1, MAPK14, ESR1, DRD2, EGFR and CDKN1B. Conclusion These preliminary results suggest that tamoxifen may provide clinical benefit in residual NF-PitNETs, particularly those expressing ERβ. Further validation studies are required to confirm efficacy and identify predictive molecular markers.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Nonfunctioning pituitary neuroendocrine tumors, nonfunctioning pituitary adenoma, estrogen receptor, tamoxifen, immunohistochemistry, pilot trial, target prediction analysis
Subjects:	R Medicine > RC Internal medicine > RC648 Specialties of Internal Medicine-Diseases of The Endocrine Glands. Clinical Endocrinology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Science > Department of Biotechnology Kulliyyah of Medicine > Department of Internal Medicine
Depositing User:	Dr Amalina Haydar Ali Tajuddin
Date Deposited:	17 Sep 2025 16:26
Last Modified:	17 Sep 2025 16:26
URI:	http://irep.iium.edu.my/id/eprint/123222

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