The control group received oral methotrexate (10 mg/week) combined with folic acid (10 mg/week)...Its mechanism involves suppressing key inflammatory mediators TNF-α and IL-17A, thereby activating and regulating the Wnt/β-catenin signaling pathway. This modulates serum levels of OPG and β-CTX, leading to systemic improvement in bone metabolic balance and exerting a multi-target therapeutic effect.

While HPE treatment with MTX improved body weight, biochemical, ultrastructural and biophysical changes comparing to the MTX group. Human placental extract can reduce MTX-induced nephrotoxicity in rats through boosting oxidative stress/anti-oxidant balance as it is rich with essential elements.

P2/3, N=132, Not yet recruiting, Singapore General Hospital

Among the pharmacogenetic factors influencing toxicity of commonly used B-ALL treatments, variants in the TPMT and NUDT15 genes, both involved in the metabolism of 6-mercaptopurine, represent the most robust and clinically validated predictors. Emerging evidence also links additional genetic variants to toxicities associated with other key agents used in ALL treatment regimens, including variants in SLCO1B1 associated with methotrexate-related gastrointestinal toxicity and variants in CEP72 associated with vincristine-induced neuropathy. The integration of pharmacogenomic biomarkers into clinical protocols, enabling genotype-guided dose adjustment, may represent a valuable strategy to avoid toxicity and improve overall cancer outcomes. However, further studies and innovative approaches are required to validate emerging biomarkers and facilitate their translation into routine clinical practice.

Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.

The current standard of care for induction treatment is based on high-dose methotrexate as the central component, followed by consolidating high-dose chemotherapy and autologous stem cell transplantation in eligible patients...Given the significant prognostic and therapeutic implications of the immune microenvironment, its impact should be reflected and validated in future standard risk stratifications. Integrating validated immune biomarkers with emerging immunotherapeutic strategies has the potential not only to improve individual patient outcomes but also to optimize the overall structure of care for patients with PCNSL.

CAR ameliorates MTX-induced adverse effects in the testes of rats via controlling redox balance, NO/cGMP signaling, inflammation, and steroidogenesis, with the potential of CAR to be used as a treatment to protect male reproductive function during therapy with MTX.

Doxorubicin-loaded autologous exosomes reduced A549 viability to 40.5 ± 2.0% at 200 µg/mL, compared to 64.5 ± 8.1% with heterologous exosomes, with similar trends for methotrexate and paclitaxel. Proteomic analysis revealed a shared core proteome with distinct cell-specific signatures. These findings highlight the superior delivery efficiency of autologous exosomes as precision nanocarriers.

CAP and BV exhibit promising potential for alleviating RA in rats, with their combined application showing the greatest efficacy. The antiarthritic effects may be mediated via suppression of oxidative stress and inflammation and enhancement of the antioxidant defense system in addition to the modulatory effects on MMP-1 and MMP-3 gene expression. Further clinical research is essential to evaluate their safety and effectiveness in human RA management.

It highlights the need for comprehensive, real-time risk assessment that integrates gene-environment interactions, multi-omics data, and clinical monitoring to improve precision therapy for ALL. This approach combines extended PGx profiling, transcriptomic monitoring, and clinical biomarker assessment to provide a transformative strategy for precision drug delivery.

For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants.

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: May 2026 --> Sep 2026