A 25-year-old woman with pre-existing Hashimoto's thyroiditis developed progressive bilateral nodular scleritis with anterior uveitis that proved completely refractory to high-dose corticosteroids, methotrexate, and conventional disease-modifying antirheumatic drugs, along with papilledema and granulomatous rosacea, suggesting systemic inflammation. Recognition of this molecular target enabled precision therapy with fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, combined with adalimumab, a tumor necrosis factor-alpha (TNF-α) inhibitor, resulting in complete and sustained remission of all inflammatory manifestations over 18 months of follow-up. This case underscores the critical importance of maintaining high clinical suspicion for paraneoplastic autoimmune syndromes in patients with treatment-refractory inflammatory conditions, particularly when accompanied by atypical systemic or unexplained laboratory findings, and demonstrates that molecularly targeted precision medicine approaches can transform treatment outcomes in complex paraneoplastic rheumatic disorders.

This study highlights potential metabolite signatures associated with in vitro SYK-targeted therapy in AML. These findings support future research to identify potential serum biomarkers, guiding personalized SYK inhibition strategies in AML.

Finally, we demonstrated the efficacy of TUS plus PMB therapy in a mouse model of pulmonary infection with a clinical PMB-resistant K. pneumoniae isolate. In all, this work discovers a promising drug combination strategy based on PMB and TUS and underlies the special mode of action that involves inhibiting the activity of NagA.

P1, N=36, Recruiting, University of California, San Diego | Trial primary completion date: Jun 2027 --> Dec 2027

Lower-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are commonly managed with erythropoiesis-stimulating agents, luspatercept, or hypomethylating agents. There were no dose-limiting toxicities. Although safe, fostamatinib demonstrated no clinical benefit, underscoring the need for alternative strategies to modulate inflammatory signaling in MDS/CMML.

Our results identify PHF23 as a critical oncogenic driver in glioma and support the PHF23-RPS for risk stratification. Entospletinib may offer a potential immunomodulatory option for high-risk gliomas.

P2/3, N=110, Active, not recruiting, Hutchison Medipharma Limited | Trial primary completion date: Sep 2026 --> Nov 2025 | Recruiting --> Active, not recruiting

Dual targeting of FLT3/SYK (TAK-659) and the proteasome (Ixazomib) showed strong synergy across genetically defined AML subsets, irrespective of FLT3 mutant status. These findings define a therapeutically targetable axis linking FLT3/SYK/β-catenin signaling to stress adaptation, provide a mechanistic basis for combinatorial targeting in high-risk AML. Trial registration: NCT04079738, Date of registration 03 September 2019.

P1, N=18, Completed, Hutchmed | Recruiting --> Completed

P1, N=54, Completed, Hutchmed | Recruiting --> Completed | Trial primary completion date: Feb 2026 --> Nov 2025

P2, N=40, Not yet recruiting, Inova Health Care Services | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: May 2026 --> May 2027

P1, N=18, Recruiting, Hutchmed