KDM1A (Lysine Demethylase 1A)

Concurrently, breakthroughs have been achieved in optimizing structure, mechanism of action, dual-target strategies, selectivity and safety, and indications. Future efforts should focus on further validating dual-target strategies, and elucidating binding mechanisms to advance their application as a core targeted therapy in epigenetics for more malignant tumors therapy.

Several PROTAC therapies are now in AML trials. LSD1-targeted degradation is promising, but further research is needed to confirm its safety, overcome resistance, and identify optimal drug combinations for AML treatment.

A coordinated mechanism where uterine cancer cells adaptively up-regulate RFVTs, FADS, and LSD1 to meet their metabolic demands was revealed. These results provide insights into the metabolic vulnerabilities of uterine cancer and propose Rf metabolism and flavin-dependent processes as potential therapeutic targets.

Glioblastoma stem cell (GSC) lines and normal human astrocytes (NHAs) were treated with catalytic LSD1 inhibitors, NCD38 and bomedemstat, and the LSD1 scaffolding inhibitor, seclidemstat alone and in combination with kinase inhibitors, including osimertinib, afatinib, and ulixertinib. Combined treatment with NCD38 and osimertinib in glioblastoma-bearing mice delayed tumor growth and improved survival outcomes. These findings provide a rationale for further investigation of combination therapies of catalytic inhibitors of LSD1 and EGFR and dual-targeted inhibitors to overcome resistance and improve outcomes.

Here we address a long-standing question in the field surrounding LSD1 and define the distinct enzymatic and nonenzymatic functions of LSD1 in Ewing sarcoma. In doing so, we have created a robust data set using genetic and pharmacological techniques in multiple models to thoroughly characterize LSD1 function in Ewing sarcoma cell lines.

Additionally, Corin treatment upregulated FDX1 expression to trigger Cuproptosis, which suppressed HCC proliferation. Conclusively, Corin possesses potential application as a novel and effective therapeutic option for HCC that simultaneously inhibits KDM1A and HDAC1 expression.

KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment.

Inhibiting LSD1 in GC upregulates TNFSF14 expression, which in turn promotes T cell proliferation, CD8+ activation, and chemotaxis. This enhancement of T cell-mediated anti-tumor immunity is further amplified when LSD1 inhibitors are used alongside PD-(L)1 blockers, facilitating the activation of CD8+ T cells in the spleen and improving leukocyte infiltration in the tumor.

Importantly, KDM inhibitors can be used as modulators of anti-cancer immune response and sensitivity to radiation and chemotherapy. This narrative review aims to present the most recent evidence documenting the anti-cancer potential of KDM inhibitors.

These findings reveal a novel KDM1A-RNF81-KLF4 regulatory axis in GC and highlight RNF81 as a potential therapeutic target for GC treatment. Targeting this pathway may offer promising strategies to improve outcomes for GC patients.

In this review, we summarize novel findings on the epigenomic landscape in the context of TRβ in thyroid malignancy, including the identification of previously unrecognized TRβ interactors and the mapping of nine distinct functional protein communities that constitute the TRβ interactome in thyroid cells. We also explore how targeting TRβ interactors using existing epigenetic enzyme inhibitors-such as HDAC, LSD1, and BET inhibitors-in combination with TRβ agonists, may work synergistically to reprogram tumor epigenetics and suppress oncogenic transcriptional programs.

Finally, we reviewed the rarely discussed but critical condition of immune reconstitution inflammatory syndrome (IRIS) following CS treatment, including a case from our own experience. IRIS should be kept in mind when initiating treatment for CS patients with extremely high serum cortisol levels.