Universität zu Köln

Smarsly, D., Kreuzberg, N., Langhorst, C., Scheffler, M. ORCID: 0000-0002-9031-1368, Siebolts, U., Lennartz, S., Koll, P., Glaser, A.-C. and Franklin, C. ORCID: 0000-0001-9142-5423 (2026). Montelukast as a novel therapeutic approach in metastatic uveal melanoma harboring a CYSLTR2 mutation: a translational case report. ESMO Open, 11 (1). pp. 1-4. Elsevier. ISSN 2059-7029

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Abstract

[Artikel-Nr.: 105921] Background: Uveal melanoma (UM), the most common primary intraocular malignancy in adults, has limited systemic treatment options in the metastatic setting. Recent insights into cysteinyl leukotriene receptors (CysLTRs)―particularly CYSLTR2 mutations (prevalence 2%-4%)―suggest new therapeutic approaches for patients who progress despite standard therapies. Case: We report the case of a 59-year-old male with metastatic UM harboring a CYSLTR2 mutation. The patient experienced progression after multiple systemic treatments, including immune checkpoint inhibitors (ipilimumab/ nivolumab, pembrolizumab), chemotherapy (dacarbazine, gemcitabine/treosulfan), and local radiotherapy. Lacking human leukocyte antigen-A*02:01, he was ineligible for tebentafusp. In November 2022, next-generation sequencing identified a CYSLTR2 mutation. Based on molecular tumor board recommendation, off-label treatment with montelukast, a selective CysLT1 receptor antagonist, was initiated in March 2024. At that time, the patient had widespread metastases. Montelukast led to sustained disease stabilization for >12 months, with excellent tolerability and no reported adverse events. The observed effect may be explained by inhibition of CYSLTR1 and modulation of CYSLTR2 signaling in the mutated receptor context. Conclusion: This is the first published case suggesting a potential role for leukotriene receptor antagonists in CYSLTR2- mutant UM. These findings support further preclinical and clinical investigation of montelukast as a repurposed therapy in this challenging disease entity

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Smarsly, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuzberg, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langhorst, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheffler, M. UNSPECIFIED https://orcid.org/0000-0002-9031-1368 UNSPECIFIED Siebolts, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lennartz, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koll, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Glaser, A.-C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franklin, C. UNSPECIFIED https://orcid.org/0000-0001-9142-5423 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-812731
Identification Number:	10.1016/j.esmoop.2025.105921
Journal or Publication Title:	ESMO Open
Volume:	11
Number:	1
Page Range:	pp. 1-4
Number of Pages:	4
Date:	January 2026
Publisher:	Elsevier
ISSN:	2059-7029
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Dermatologie > Klinik und Poliklinik für Dermatologie und Venerologie Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie Faculty of Medicine > Radiologische Diagnostik > Institut und Poliklinik für Radiologische Diagnostik Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO)
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language uveal melanoma, CYSLTR2 mutation, montelukast, leukotriene receptor, targeted therapy, case report, drug repurposing English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81273