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.

P3, N=257, Active, not recruiting, Karyopharm Therapeutics Inc | Recruiting --> Active, not recruiting

P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026

P1, N=22, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Nov 2025 | Trial primary completion date: Jun 2026 --> Nov 2025

Unbiased combinatorial screening reveals co-inhibition of nuclear export and translation initiation as a vulnerability in metastatic castration-resistant prostate cancer. Dual targeting of XPO1 and EIF4A1 drives synergistic collapse of oncogenic protein networks, including AR/AR-V7 signaling, to overcome key resistance mechanisms and induce potent antitumor responses across heterogeneous models. Notably, these effects are achieved at substantially reduced doses using clinically tractable agents, defining a mechanistically grounded therapeutic strategy poised for rapid clinical translation.