ERK/MAPK signaling in MPN

Current understanding

To be populated as evidence accumulates.

Evidence log

• 2026-07-20 — Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia: Phase II trial of single-agent trametinib (MEK1/2 inhibitor) in relapsed/refractory JMML tests MAPK-cascade blockade as monotherapy in a RAS-driven pediatric MDS/MPN overlap disease, complementing the frontline trametinib+azacitidine study on the same page. (novelty: 3)
• 2026-09-04 — A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia: Phase I/II trial of trametinib (MEK1/2 inhibitor) + azacitidine in newly diagnosed JMML (with fludarabine/cytarabine added for high-risk disease) targets the RAS–MAPK axis upstream of ERK, extending MAPK-cascade blockade + hypomethylation to a pediatric RAS-driven MPN/MDS overlap disease. (novelty: 3)
• 2026-02-13 — Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms: ASTX029 (ERK inhibitor) + ASTX727 (oral decitabine/cedazuridine) phase I/II in RAS pathway-mutant MDS and MDS/MPN extends ERK/MAPK targeting to a genomically defined subpopulation, pairing pathway blockade with hypomethylation rather than JAK inhibition. (novelty: 4)
• 2026-04-03 — A Study of Ruxolitinib in Combination With Ulixertinib in People With Myelofibrosis: Phase I/II trial of ruxolitinib + ulixertinib (selective ERK1/2 inhibitor) in myelofibrosis directly tests the hypothesis that ERK/MAPK reactivation is a downstream escape pathway from JAK inhibition, marking the first clinical-stage dual JAK + ERK1/2 blockade strategy in MPN. (novelty: 4)

Open questions

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