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Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma
Rachel D Dreher1,2, Emily R Theisen1,2,3
1Abigail Wexner Research Institute, Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, OH, United States.
Abstract:
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.
Insights
Histone lysine specific demethylase 1 (LSD1) is a potential therapeutic target in sarcomas. This review explores LSD1
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Sarcomas are complex tumors with diverse drivers, hindering effective treatment development.
- Understanding sarcoma cell of origin and biological drivers is crucial for new therapies.
- Histone lysine specific demethylase 1 (LSD1) is overexpressed in several sarcomas, presenting a therapeutic target.
Purpose of the Study:
- To review the known functions of LSD1 in various sarcomas.
- To identify knowledge gaps and emerging themes regarding LSD1's role in bone and soft tissue sarcomas.
- To discuss the clinical development of LSD1 inhibitors for sarcoma treatment.
Main Methods:
- Literature review of LSD1 function in sarcomas.
- Analysis of existing data on LSD1 overexpression and its role in sarcoma pathogenesis.
- Examination of current clinical trials involving LSD1 inhibitors in sarcoma patients.
Main Results:
- LSD1 plays a context-dependent role in gene regulation via histone modification.
- LSD1's specific functions and interactions in bone and soft tissue sarcomas are not fully understood.
- Sarcomas are being included in early-phase clinical trials for LSD1 inhibitors.
Conclusions:
- LSD1 is a significant molecular driver in bone and soft tissue sarcomas.
- Further research is needed to elucidate LSD1's precise roles and therapeutic potential in different sarcoma subtypes.
- LSD1 inhibitors represent a promising avenue for sarcoma treatment, warranting continued clinical investigation.
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