tofacitinib

Overview

Tofacitinib is a small-molecule inhibitor of JAK1 and JAK3 (with lesser activity against JAK2 and TYK2), blocking downstream STAT signaling. It is FDA-approved for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis. In oncology it has been investigated in hematologic malignancies driven by constitutive JAK-STAT pathway activation, including T-cell lymphomas with JAK3 mutations.

Evidence in the corpus

• Tofacitinib (JAK1/3 inhibitor) was active against HUT78 CTCL cells harboring a JAK3 p.Ala573Val activating mutation alongside ruxolitinib; MEK1/2 inhibition and NFAT inhibition had only modest effects in the same lines, supporting genotype-stratified JAK inhibitor use in JAK3/STAT3/SH2B3-mutant CTCL PMID:26551667

Resistance mechanisms

Cancer types (linked)

• SS — Sézary syndrome; activity observed in JAK3-mutant cell line model

Sources

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