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selumetinib + sirolimus
- Development stage
- Unknown
- Lead developer
- Sarcoma Alliance for Research through Collaboration
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
**Selumetinib + sirolimus** is an investigational oral combination therapy pairing the **MEK inhibitor selumetinib (AZD6244)**, which blocks the MAPK/ERK signaling pathway downstream of RAS/RAF, with the **mTOR inhibitor sirolimus (rapamycin)**, which inhibits the PI3K/AKT/mTOR pathway to suppress cell growth and proliferation. Developed for advanced sarcomas, particularly **unresectable or metastatic malignant peripheral nerve sheath tumors (MPNST)** associated with neurofibromatosis type 1 (NF1) or sporadic cases, the regimen targets synergistic pathway inhibition to overcome resistance seen with single agents. Administered as selumetinib 50 mg twice daily continuously and sirolimus 4 mg daily (with a 12 mg loading dose on cycle 1 day 1) in 28-day cycles, it is being evaluated in phase 2 trials like SARC031 for clinical benefit rate, progression-free survival, and toxicity profile, showing promise in NF1-MPNST where standard chemotherapies often fail.[1][4][7]
- Brand names
- KoselugoRapamune
- Other names
- selumetinib and sirolimusAZD6244 + rapamycinselumetinib and sirolimus combination
02
Targets
mTOR (Mammalian target of rapamycin kinase)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)
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