Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma
Abstract: Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for nov...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925001351 |
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| author | Deniz Özistanbullu Raphael Wilhelm Gabi Reichenbach Monika Doll Karola Bahrami Nadja Zöller Frank Schnütgen Anke König Theresia Scheller Lars Winkler Pascal Spahn Manuel Jäger Jan P. Nicolay Josef Pfeilschifter Bastian Schilling Roland Kaufmann Alexander Koch Stefan Kippenberger Johannes Kleemann Markus Meissner |
| author_facet | Deniz Özistanbullu Raphael Wilhelm Gabi Reichenbach Monika Doll Karola Bahrami Nadja Zöller Frank Schnütgen Anke König Theresia Scheller Lars Winkler Pascal Spahn Manuel Jäger Jan P. Nicolay Josef Pfeilschifter Bastian Schilling Roland Kaufmann Alexander Koch Stefan Kippenberger Johannes Kleemann Markus Meissner |
| author_sort | Deniz Özistanbullu |
| collection | DOAJ |
| description | Abstract: Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. Similar to other non-Hodgkin lymphomas (NHLs), MF and SS have a greater incidence rate in males than females. The endocrine contribution to this sex difference is unknown. Although several studies could show a potential role of estrogen receptor β (ERβ) on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing noncancerous skin cells. Liquid chromatography with tandem mass spectrometry analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 than normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly Monomethyl auristatin E. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications. |
| format | Article |
| id | doaj-art-3ffcd0102fe24dd48db60aec900b1f24 |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-3ffcd0102fe24dd48db60aec900b1f242025-08-20T03:05:42ZengElsevierBlood Advances2473-95292025-06-019112651266210.1182/bloodadvances.2024015132Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphomaDeniz Özistanbullu0Raphael Wilhelm1Gabi Reichenbach2Monika Doll3Karola Bahrami4Nadja Zöller5Frank Schnütgen6Anke König7Theresia Scheller8Lars Winkler9Pascal Spahn10Manuel Jäger11Jan P. Nicolay12Josef Pfeilschifter13Bastian Schilling14Roland Kaufmann15Alexander Koch16Stefan Kippenberger17Johannes Kleemann18Markus Meissner19Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; Correspondence: Deniz Özistanbullu, Department of Dermatology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany;Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Molecular Hematology and LOEWE Center for Cell and Gene Therapy, Goethe University Medical School, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyExperimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, GermanyExperimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin, GermanyDepartment of Dermatology, Städtisches Klinikum Karlsruhe, Karlsruhe, GermanyDepartment of Dermatology, Städtisches Klinikum Karlsruhe, Karlsruhe, GermanyDepartment of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of General Pharmacology and Toxicology, Goethe University Hospital and Goethe University Frankfurt, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyDepartment of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, Frankfurt, GermanyAbstract: Cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. Similar to other non-Hodgkin lymphomas (NHLs), MF and SS have a greater incidence rate in males than females. The endocrine contribution to this sex difference is unknown. Although several studies could show a potential role of estrogen receptor β (ERβ) on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing noncancerous skin cells. Liquid chromatography with tandem mass spectrometry analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 than normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly Monomethyl auristatin E. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications.http://www.sciencedirect.com/science/article/pii/S2473952925001351 |
| spellingShingle | Deniz Özistanbullu Raphael Wilhelm Gabi Reichenbach Monika Doll Karola Bahrami Nadja Zöller Frank Schnütgen Anke König Theresia Scheller Lars Winkler Pascal Spahn Manuel Jäger Jan P. Nicolay Josef Pfeilschifter Bastian Schilling Roland Kaufmann Alexander Koch Stefan Kippenberger Johannes Kleemann Markus Meissner Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma Blood Advances |
| title | Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma |
| title_full | Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma |
| title_fullStr | Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma |
| title_full_unstemmed | Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma |
| title_short | Estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous T-cell lymphoma |
| title_sort | estrogen receptor β stimulation as a possible novel therapeutic target for cutaneous t cell lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925001351 |
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