methotrexate

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.

Although agents such as lenalidomide and Bruton's tyrosine kinase(BTK) inhibitors have demonstrated efficacy in relapsed/refractory (R/R)PVRL, their role in treatment-naïve patients remains unclear. In conclusion, the combination of Orelabrutinib, rituximab, and intravitreal MTX is a feasible therapeutic strategy for PVRL. Our findings may contribute to a potential paradigm shift in the management of this rare disease.

Drug sensitivity analysis demonstrated that high TYMS expression positively correlated with sensitivity to Afatinib and Gefitinib, but negatively correlated with Methotrexate and Vorinostat. In conclusion, TYMS is upregulated in LUAD and may serve as an independent prognostic biomarker and therapeutic target.

P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Jun 2026 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2028

We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context...Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings.

Importantly, our AI-aided approach not only identified this axis but also predicted its vulnerability to metabolic intervention: both methotrexate treatment and LDHA knockdown restored metabolic balance, reversed T‑cell exhaustion, and suppressed tumor growth. These findings highlight the power of ML in uncovering multi-targetable metabolic-immune networks and in guiding therapeutic strategies to overcome immune evasion in DLBCL.

The primary endpoint of the SELECT-SWITCH trial was met, with a higher percentage of patients with active RA who switched to upadacitinib after first TNFi failure achieving DAS28-CRP ≤3.2 at 12 weeks than those cycling to a second TNFi, adalimumab, with generally similar safety profiles.

The patient initially received 2 cycles of rituximab combined with high-dose methotrexate chemotherapy...Subsequently, the regimen was adjusted to 6 cycles of cytarabine combined with temozolomide chemotherapy followed by radiotherapy for the intracranial lesion...Up to the date of follow-up, the patient's condition was stable without recurrence. Combined with literature review, this article discusses the possible mechanisms of the coexistence of dual-subtype DLBCL (clonal evolution or biclonal origin), the potential pathways of temporal muscle metastasis and the impact of subtype differences on treatment response, which provides clinical reference for the diagnosis and individualized treatment of such rare cases.

P2/3, N=1124, Active, not recruiting, St. Anna Childrens Cancer Research Institute GmbH | Not yet recruiting --> Active, not recruiting

P1, N=48, Recruiting, Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting --> Recruiting

In contrast, chemotherapy-induced seizures, particularly those associated with high-dose methotrexate, arise from disrupted folate metabolism, intracellular oxidative stress, and subsequent N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. We provide a comparative analysis of these pathways, integrating current evidence on pharmacogenomic susceptibility-including polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and drug transporter genes-as well as epigenetic factors. By synthesizing these molecular insights, we propose a mechanistic framework for precise clinical differentiation, which may inform biomarker-driven diagnostic approaches and targeted neuroprotective strategies in this vulnerable population.

ASCT was associated with the most durable survival among consolidation strategies after R-MVP induction. These findings, derived from a large real-world, multi-institutional cohort, support ASCT as the preferred consolidation for eligible patients while underscoring the heterogeneity of current practice and the need for prospective validation.