PI3K-AKT signaling

Current understanding

To be populated as evidence accumulates.

Evidence log

• 2026-06-18 — RAD001 in Relapsed or Refractory AML, ALL, CML in Blastic-Phase, Agnogenic Myeloid Metaplasia, CLL, T-Cell Leukemia, or Mantle Cell Lymphoma: Phase I/II dose-escalation trial of RAD001 (everolimus, mTOR inhibitor) in relapsed/refractory hematologic malignancies including agnogenic myeloid metaplasia (MF) targets the downstream mTOR node of PI3K-AKT signaling as monotherapy, complementing upstream PI3Kδ-targeted combinations. (novelty: 3)
• 2026-05-19 — TGR-1202 + Ruxolitinib PMF PPV-MF PET-MF MDS/MPN Polycythemia Vera Resistant to Hydroxyurea: Phase 1 open-label trial of TGR-1202 (PI3Kδ inhibitor) + ruxolitinib across PV (HU-resistant), PMF, PPV-MF, PET-MF, and MDS/MPN adds a third PI3Kδ-selective agent (alongside roginolisib and IOA-244) to the PI3K-AKT + JAK-STAT dual-blockade combination portfolio, and uniquely extends this strategy beyond MF into PV and MDS/MPN overlap. (novelty: 3)
• 2026-03-30 — A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers: Phase 1 trial of IOA-244 (selective PI3Kδ inhibitor) as monotherapy and combined with ruxolitinib in PMF further operationalizes PI3Kδ as a clinically targetable arm of PI3K-AKT signaling parallel to JAK-STAT, joining roginolisib + ruxolitinib in the post-JAKi combination portfolio. (novelty: 4)
• 2026-04-21 — Therapeutic RSK1 Targeting in Myelofibrosis: PMD-026 (RSK1 inhibitor) phase Ib trial in MF targets a kinase downstream of RAS/MAPK/ERK that converges with PI3K-AKT on mTOR/translational output, suggesting parallel therapeutic strategies against AKT-axis hyperactivation in MPN. (novelty: 4)
• 2026-04-27 — A Study of Roginolisib in Combination With Ruxolitinib in Patients With Myelofibrosis (MF) Who Are Unresponsive to JAK Inhibitors: cross-connection with jak-stat-signaling: Roginolisib (PI3K-delta) + ruxolitinib trial in JAKi-unresponsive MF operationalizes the PI3K-AKT axis as a therapeutically targetable parallel pathway to JAK-STAT, complementing preclinical PITPβ-AKT findings. (novelty: 4)

Open questions

Related mechanisms