ArticlePloS one2020
The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Clinical characteristics and status of treatment of small-cell carcinoma of the ovary, hypercalcemic type in the Chinese population: a meta-analysis.Journal of gynecologic oncology · 2024Pooled it
- Preclinical proof of concept for a personalized SNAP™-TIL (Specific Neo-Antigen Peptides-TIL) therapy platform.Oncoimmunology · 2026Article
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Article
- ARID1A deficiency-driven reprogramming of polyamine metabolism promotes endometrial cancer malignancy and immune escape.Cell death & disease · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- DLGAP5 promotes salivary adenoid cystic carcinoma proliferation and metastasis through PI3K/AKT pathway.American journal of cancer research · 2026Article
- Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.Molecular biomedicine · 2025Review
- Computational study of chalcone-cyanopyrimidine hybrids as LSD1 inhibitors: Assessing the influence of FAD on binding affinity and inhibition.Biochemistry and biophysics reports · 2025Article
- Epigenetic Regulation of Immune Responses in Endocrine-Related Cancers and Its Role in Immunotherapy.Cancers · 2025Review
- Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.Journal of experimental & clinical cancer research : CR · 2025Review
- RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids.Cancer chemotherapy and pharmacology · 2025Article
- High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Seclidemstat (SP-2577) Induces Transcriptomic Reprogramming and Cytotoxicity in Multiple Fusion-Positive Sarcomas.Cancer research communications · 2025Article
- Histone demethylase inhibitors: developmental insights and current status.Future medicinal chemistry · 2025Review
- Loss of SMARCA4 Leads to Intron Retention and Generation of Tumor-Associated Antigens in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.Cancer research · 2025Article
- Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.Epigenetics & chromatin · 2025Review
- Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.Acta pharmacologica Sinica · 2025Article
- Current advances and future directions in targeting histone demethylases for cancer therapy.Molecules and cells · 2025Review
- Role of the NuRD complex and altered proteostasis in cancer cell quiescence.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations of the SWI/SNF chromatin remodeling complex occur in 20% of all human cancers, including ovarian cancer. Approximately half of ovarian clear cell carcinomas (OCCC) carry mutations in the SWI/SNF subunit ARID1A, while small cell carcinoma of the ovary hypercalcemic type (SCCOHT) presents with inactivating mutations of the SWI/SNF ATPase SMARCA4 alongside epigenetic silencing of the ATPase SMARCA2. Loss of these ATPases disrupts SWI/SNF chromatin remodeling activity and may also interfere with the function of other histone-modifying enzymes that associate with or are dependent on SWI/SNF activity. One such enzyme is lysine-specific histone demethylase 1 (LSD1/KDM1A), which regulates the chromatin landscape and gene expression by demethylating proteins such as histone H3. Cross-cancer analysis of the TCGA database shows that LSD1 is highly expressed in SWI/SNF-mutated tumors. SCCOHT and OCCC cell lines have shown sensitivity to the reversible LSD1 inhibitor SP-2577 (Seclidemstat), suggesting that SWI/SNF-deficient ovarian cancers are dependent on LSD1 activity. Moreover, it has been shown that inhibition of LSD1 stimulates interferon (IFN)-dependent anti-tumor immunity through induction of endogenous retroviral elements and may thereby overcome resistance to checkpoint blockade. In this study, we investigated the ability of SP-2577 to promote anti-tumor immunity and T-cell infiltration in SCCOHT and OCCC cell lines. We found that SP-2577 stimulated IFN-dependent anti-tumor immunity in SCCOHT and promoted the expression of PD-L1 in both SCCOHT and OCCC. Together, these findings suggest that the combination therapy of SP-2577 with checkpoint inhibitors may induce or augment immunogenic responses of SWI/SNF-mutated ovarian cancers and warrants further investigation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.