Jakafi (ruxolitinib)

P3, N=430, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2027 --> Jun 2027

P2, N=40, Recruiting, Children's Hospital Medical Center, Cincinnati | Trial completion date: Nov 2025 --> Nov 2028 | Trial primary completion date: Nov 2025 --> Nov 2028

Despite partial responses to topical therapies, oral prednisone, and methotrexate, the disease persisted, highlighting therapeutic challenges. This case underscores the importance of molecular profiling in PCAECTCL and suggests potential utility for JAK inhibitors like ruxolitinib.

Notwithstanding substantial concerns about thrombotic risk due to positive phospholipid antibodies in the context of ruxolitinib treatment, thrombotic events were avoided with patient compliance to low-dose aspirin therapy. This case highlighted that the male patients aged over 50 years presenting with chondritis, refractory autoinflammatory manifestations, and/or unexplained hematological abnormalities, clinicians should consider bone marrow evaluation and UBA1 gene testing to promptly identify VEXAS syndrome, enabling early personalized treatment and improved outcomes.

Treatment also decreased VEGF secretion in both monocultures and HS-5 stromal co-cultures and induced IL-1β in co-cultures. These findings demonstrate that STK405759 exerts potent cytotoxic activity, disrupts microtubules, modulates STAT1 signaling, reduces VEGF secretion, and induces a distinct cytokine profile, while synergizing with ruxolitinib, supporting its further preclinical development as a potential therapeutic strategy in myeloproliferative neoplasms.

We knocked down THBS1 in rat (BRL, BRL-3A) and human (THLE-2) hepatocytes using siRNA and applied Ruxolitinib to inhibit the JAK2/STAT3 pathway, further clarifying the role of THBS1 in this signaling process...In addition, plasma ELISA revealed that the concentration of THBS1 in plasma increased with increasing radiation dose and degree of RILI, which was consistent with the expression level in the liver tissue. This study provides new insights into the pathogenesis of RILI, and identifies THBS1 as a potential biomarker for RILI diagnosis and monitoring.

Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.

P1, N=20, Not yet recruiting, City of Hope Medical Center

MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients...Elevated levels of circulating RANTES correlated with ET plasma-induced proplatelet formation, which was partially reverted by RANTES receptor CCR5 antagonist Maraviroc, indicating RANTES is involved in this process. These findings indicate that, in addition to clonal mutations, extrinsic inflammatory mediators play a direct role in MF and ET megakaryocyte abnormalities. The distinct cytokine profile could potentially be useful for the development of targeted therapies.

Additionally, fostamatinib inhibited PDAC cell proliferation even in the absence of viral infection, while ruxolitinib did not. Our data suggest that fostamatinib may be repurposed as an effective drug that enhances OV therapy in PDAC by promoting OV replication and suppressing tumor growth.

P1/2, N=39, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2029 --> Jan 2030 | Trial primary completion date: Oct 2027 --> Jan 2028

P4, N=40, Recruiting, The First Affiliated Hospital of Soochow University