ArticleOncogene2022
RB1 loss in castration-resistant prostate cancer confers vulnerability to LSD1 inhibition.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- KDM7A and KDM1A inhibition suppresses tumour promoting pathways in prostate cancer.Molecular oncology · 2026Article
- Mechanistic insights and molecular therapy for neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Article
- Prognostic Significance ofJCO precision oncology · 2025Article
- Quinazoline Derivative kzl052 Suppresses Prostate Cancer by Targeting WRN Helicase to Stabilize DNA Replication Forks.International journal of molecular sciences · 2025Article
- Emerin Dysregulation Drives the Very-Small-Nuclear Phenotype and Lineage Plasticity That Associate with a Clinically Aggressive Subtype of Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Heterogeneous Responses to High-Dose Testosterone in Castration-Resistant Prostate Cancer Tumors with Mixed Rb-Proficient and Rb-Deficient Cells.Molecular cancer therapeutics · 2025Article
- Emerging Therapeutic Targets of Neuroendocrine Prostate Cancer.Current oncology reports · 2025Review
- The Emerging Predictive and Prognostic Role of Aggressive-Variant-Associated Tumor Suppressor Genes Across Prostate Cancer Stages.International journal of molecular sciences · 2025Review
- Interactions between key genes and pathways in prostate cancer progression and therapy resistance.Frontiers in oncology · 2025Review
- Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.Cell death and differentiation · 2024Article
- Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy.Cancers · 2024Review
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- The molecular determinants of phenotypic plasticity in homeostasis and neoplasia.Cancer heterogeneity and plasticity · 2024Article
- Analysis of genetic biomarkers, polymorphisms in ADME-related genes and their impact on pharmacotherapy for prostate cancer.Cancer cell international · 2023Review
- Review
- LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function.JCI insight · 2023Article
- Demethylation of EHMT1/GLP Protein Reprograms Its Transcriptional Activity and Promotes Prostate Cancer Progression.Cancer research communications · 2023Article
- LSD1 Inhibition Disrupts Super-Enhancer-Driven Oncogenic Transcriptional Programs in Castration-Resistant Prostate Cancer.Cancer research · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Genomic loss of RB1 is a common alteration in castration-resistant prostate cancer (CRPC) and is associated with poor patient outcomes. RB1 loss is also a critical event that promotes the neuroendocrine transdifferentiation of prostate cancer (PCa) induced by the androgen receptor (AR) signaling inhibition (ARSi). The loss of Rb protein disrupts the Rb-E2F repressor complex and thus hyperactivates E2F transcription activators. While the impact of Rb inactivation on PCa progression and linage plasticity has been previously studied, there is a pressing need to fully understand underlying mechanisms and identify vulnerabilities that can be therapeutically targeted in Rb-deficient CRPC. Using an integrated cistromic and transcriptomic analysis, we have characterized Rb activities in multiple CRPC models by identifying Rb-directly regulated genes and revealed that Rb has distinct binding sites and targets in CRPC with different genomic backgrounds. Significantly, we show that E2F1 chromatin binding and transcription activity in Rb-deficient CRPC are highly dependent on LSD1/KDM1A, and that Rb inactivation sensitizes CRPC tumor to the LSD1 inhibitor treatment. These results provide new molecular insights into Rb activity in PCa progression and suggest that targeting LSD1 activity with small molecule inhibitors may be a potential treatment strategy to treat Rb-deficient CRPC.
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Registered trials
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.