thioguanine

P3, N=9350, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2028 --> Mar 2026

P2, N=222, Recruiting, National Cancer Institute (NCI) | Phase classification: P3 --> P2

P2, N=171, Completed, Incyte Corporation | Active, not recruiting --> Completed

Pharmacological inhibitors of specific USPs, such as pimozide, trifluoperazine, rottlerin, 6-thioguanine, and costunolide, are highlighted for their potential to inhibit proliferation, metastasis, induce apoptosis, and circumvent therapy resistance across breast cancer subtypes (triple-negative and HER-2 positive). The review highlights the complex and often contradictory roles of USPs in breast cancer and points to the immense promise of targeting these enzymes to develop new and efficacious anticancer therapies.

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

In KRAS-mutant cancer models, trametinib treatment caused dysregulation of the purine biosynthetic pathway driven by reductions in enzyme GART. This induced vulnerability nominated purine analog 6-thioguanine as a synergistic partner...In vivo, the treatment significantly increases overall survival without systemic toxicity. Integrating drug-induced multi-omic changes with functional screening identifies therapeutic strategies, supporting the use of purine analogs with MEK inhibitors for KRAS-mutant tumors.

Allopurinol co-treatment reduces toxicity while maintaining therapeutic efficacy at lower 6-MP doses. The proposed model warrants prospective evaluation for clinical relevance confirmation.

P3, N=5951, Recruiting, Children's Oncology Group | Trial completion date: Mar 2030 --> Mar 2032 | Trial primary completion date: Mar 2030 --> Mar 2032

P1/2, N=18, Completed, Kristoffer Rohrberg | Recruiting --> Completed | N=39 --> 18

Protein-protein interaction networks indicate that these variations are involved in nucleotide metabolism and pharmacological responses, confirming their role in thiopurine resistance. In summary, NT5C2 and PRPS1 gene variations may act as potential biomarkers for resistance and hence require more experimental validation of VUS to determine their significance.

P2/3, N=1708, Not yet recruiting, Children's Oncology Group | Initiation date: Mar 2026 --> Jun 2026

High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing.