mercaptopurine

After 75 mg/m2/day mercaptopurine, myelosuppression necessitated a three-week delay prior to the next phase of therapy. With 60 mg/m2/day thioguanine in a subsequent phase of therapy, she was admitted twice for fever and neutropenia...In a larger cohort sequenced for suspicion of rare genetic disease, the frequency of NUDT15*6 was 0.15% among 1011 unrelated individuals. This brief report supports the recent update that patients with the NUDT15*1/*6 genotype should be classified as intermediate metabolizers.

P2, N=32, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P2, N=90, Not yet recruiting, SWOG Cancer Research Network

P2, N=25, Recruiting, University of Chicago | Suspended --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

The TPMT and NUDT15 genes influence the side effects of 6-MP medications. Patients who have variations in both genes are at a higher risk of experiencing toxicity. High levels of 6-TGN are associated with TPMT variants, whereas low levels are linked to NUDT15 variants. This could facilitate more precise monitoring of toxicity.

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.

Furthermore, pharmacogenomic analysis identified candidate small molecules, such as MK-886 and mercaptopurine, as potential therapeutic options. Our findings transition HCCS from a computational biomarker to a functionally validated regulator of breast cancer cell survival. By linking its systemic immunometabolic impact with its direct role in cell cycle control, this study identifies HCCS as a promising therapeutic target and a reliable prognostic indicator in BRCA.

P3, N=5949, Completed, National Cancer Institute (NCI) | Trial completion date: Oct 2026 --> Mar 2026 | Active, not recruiting --> Completed

P1, N=24, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | Trial completion date: May 2026 --> Apr 2027 | Trial primary completion date: May 2026 --> Apr 2027

Clinical variables included the median weekly 6-mercaptopurine (6-MP) dose (mg/m2, time-weighted) and duration of 6-MP dose interruptions...This real-world study demonstrates that suboptimal median 6-MP dosing and prolonged dose interruptions during maintenance are significantly associated with thiopurine resistance and MMR deficiency-related mutational signatures at relapse. These findings underscore the importance of optimised dose intensity and minimal interruptions during maintenance therapy in paediatric B-ALL.

A total of 270 patients with CD receiving azathioprine or mercaptopurine monotherapy were retrospectively enrolled. SIGNIFICANCE STATEMENT: This study identifies plasma histidine as a pharmacometabolic biomarker of thiopurine response in Crohn disease. By linking baseline amino acid metabolism to variability in therapeutic efficacy, these findings highlight metabolic status as a determinant of drug response and support metabolomics in precision pharmacotherapy.

P3, N=9350, Completed, Children's Oncology Group | Active, not recruiting --> Completed