XPO1 inhibition impairs HR and enhances radiosensitivity by disrupting the c-Myc-RAD51/CHEK1 axis. These findings support prospective evaluation of KPT-330-based radiosensitization in R/R ENKTL.

Inhibition of XPO1 with KPT-330 suppresses nuclear R-loop export and its localization into CCFs, attenuates the SASP, mitigates age-associated inflammation and extends healthspan. These findings reveal nuclear export of R-loops as a potential target for suppressing age-associated inflammation.

Continued progress in biomarker-driven strategies and rational combination therapies is expected to further refine personalized treatment approaches and improve outcomes for patients with advanced liposarcoma.

The combined treatment effectively eliminates NPM1-mutated AML cell lines and primary human AML cells in vitro and in vivo. This study reveals an ESCO2 deficiency-induced aberrant epigenetic landscape via SMC3 hypoacetylation and identifies a potential therapeutic strategy for NPM1-mutated AML.

Despite limited sample size, XPORT-MF-035 provides descriptive data on the safety, tolerability, and biological activity of selinexor monotherapy in previously treated MF, supporting further evaluation in this population. ClinicalTrials.gov identifier: NCT04562870.

Mechanistically, KPT-330 suppressed p65 phosphorylation/nuclear translocation and attenuated MAPK signaling (p38, ERK1/2, and JNK), thereby downregulating osteoclastogenic transcription factors c-Fos and NFATc1. These findings establish XPO1 inhibition as a potential dual-action strategy targeting osteoclast-mediated bone-cartilage crosstalk in OA.

P2, N=15, Not yet recruiting, Zhongshan Hospital (Xiamen), Fudan University

P2, N=27, Recruiting, Duke University | Trial primary completion date: Apr 2026 --> Dec 2026

Our findings position p300 as a central architect of pathogenic chromatin activation in MM. The combination of HAT inhibition (A485) and nuclear export inhibition (KPT8602) represents a novel, mechanistically rationalized therapeutic strategy to overcome epigenetic plasticity in MM.

In patients with JAK inhibitor-naïve myelofibrosis, selinexor plus ruxolitinib met its co-primary endpoint of improved SVR35 but did not meet the AbsTSS co-primary endpoint, compared with placebo plus ruxolitinib. An early OS difference was observed. The safety profile was consistent with known adverse event profiles of the individual agents.

P2, N=20, Completed, The First Affiliated Hospital of Soochow University | Recruiting --> Completed

Selinexor, an exportin 1 inhibitor to impede NPM1MU export from nucleus, enhances FTO degradation and reduces macrophage M2 polarization. This work reveals that FTO-creatine signaling plays an oncogenic role in NPM1MU AML, guiding more effective therapy strategies and clinical benefits for this distinctly leukemic entity.