Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma
Sarcomas are a diverse group of tumors with numerous oncogenic drivers, and display varied clinical behaviors and prognoses. This complexity makes diagnosis and the development of new and effective treatments challenging. An incomplete understanding of both cell of origin and the biological drivers...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1076581/full |
| _version_ | 1828071835371044864 |
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| author | Rachel D. Dreher Rachel D. Dreher Emily R. Theisen Emily R. Theisen Emily R. Theisen |
| author_facet | Rachel D. Dreher Rachel D. Dreher Emily R. Theisen Emily R. Theisen Emily R. Theisen |
| author_sort | Rachel D. Dreher |
| collection | DOAJ |
| description | Sarcomas are a diverse group of tumors with numerous oncogenic drivers, and display varied clinical behaviors and prognoses. This complexity makes diagnosis and the development of new and effective treatments challenging. An incomplete understanding of both cell of origin and the biological drivers of sarcomas complicates efforts to develop clinically relevant model systems and find new molecular targets. Notably, the histone lysine specific demethylase 1 (LSD1) is overexpressed in a number of different sarcomas and is a potential therapeutic target in these malignancies. With the ability to modify histone marks, LSD1 is a key player in many protein complexes that epigenetically regulate gene expression. It is a largely context dependent enzyme, having vastly different and often opposing roles depending on the cellular environment and which interaction partners are involved. LSD1 has been implicated in the development of many different types of cancer, but its role in bone and soft tissue sarcomas remains poorly understood. In this review, we compiled what is known about the LSD1 function in various sarcomas, to determine where knowledge is lacking and to find what theme emerge to characterize how LSD1 is a key molecular driver in bone and soft tissue sarcoma. We further discuss the current clinical landscape for the development of LSD1 inhibitors and where sarcomas have been included in early clinical trials. |
| first_indexed | 2024-04-11T00:59:47Z |
| format | Article |
| id | doaj.art-6c313ca8299c437fbc3831b53a422477 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T00:59:47Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6c313ca8299c437fbc3831b53a4224772023-01-04T18:12:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10765811076581Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcomaRachel D. Dreher0Rachel D. Dreher1Emily R. Theisen2Emily R. Theisen3Emily R. Theisen4Abigail Wexner Research Institute, Center for Childhood Cancer and Blood Diseases, Nationwide Children’s Hospital, Columbus, OH, United StatesBiomedical Sciences Graduate Program, College of Medicine, the Ohio State University, Columbus, OH, United StatesAbigail Wexner Research Institute, Center for Childhood Cancer and Blood Diseases, Nationwide Children’s Hospital, Columbus, OH, United StatesBiomedical Sciences Graduate Program, College of Medicine, the Ohio State University, Columbus, OH, United StatesDepartment of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, United StatesSarcomas are a diverse group of tumors with numerous oncogenic drivers, and display varied clinical behaviors and prognoses. This complexity makes diagnosis and the development of new and effective treatments challenging. An incomplete understanding of both cell of origin and the biological drivers of sarcomas complicates efforts to develop clinically relevant model systems and find new molecular targets. Notably, the histone lysine specific demethylase 1 (LSD1) is overexpressed in a number of different sarcomas and is a potential therapeutic target in these malignancies. With the ability to modify histone marks, LSD1 is a key player in many protein complexes that epigenetically regulate gene expression. It is a largely context dependent enzyme, having vastly different and often opposing roles depending on the cellular environment and which interaction partners are involved. LSD1 has been implicated in the development of many different types of cancer, but its role in bone and soft tissue sarcomas remains poorly understood. In this review, we compiled what is known about the LSD1 function in various sarcomas, to determine where knowledge is lacking and to find what theme emerge to characterize how LSD1 is a key molecular driver in bone and soft tissue sarcoma. We further discuss the current clinical landscape for the development of LSD1 inhibitors and where sarcomas have been included in early clinical trials.https://www.frontiersin.org/articles/10.3389/fonc.2022.1076581/fullLSD1sarcomamesenchymal developmentoncogenic fusion proteinepigenetics |
| spellingShingle | Rachel D. Dreher Rachel D. Dreher Emily R. Theisen Emily R. Theisen Emily R. Theisen Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma Frontiers in Oncology LSD1 sarcoma mesenchymal development oncogenic fusion protein epigenetics |
| title | Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| title_full | Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| title_fullStr | Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| title_full_unstemmed | Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| title_short | Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| title_sort | lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma |
| topic | LSD1 sarcoma mesenchymal development oncogenic fusion protein epigenetics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1076581/full |
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