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selinexor + orelabrutinib + methotrexate + thiotepa + temozolomide
- Development stage
- Unknown
- Lead developer
- Ruijin Hospital
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination regimen is a multi-drug therapy being investigated for the treatment of relapsed or refractory primary or secondary central nervous system lymphoma (r/r CNSL). The protocol, specifically studied in the SELINA trial led by Ruijin Hospital, combines two targeted agents with a flexible chemotherapy backbone. **Selinexor** is a selective inhibitor of nuclear export (SINE) that blocks Exportin 1 (XPO1), leading to the nuclear accumulation of tumor suppressor proteins. **Orelabrutinib** is a highly selective, irreversible Bruton's tyrosine kinase (BTK) inhibitor that disrupts B-cell receptor signaling pathways essential for lymphoma cell survival. The chemotherapy component consists of either **methotrexate** (an antimetabolite inhibiting dihydrofolate reductase), **thiotepa**, or **temozolomide** (both DNA alkylating agents), chosen based on patient tolerance and prior resistance. This combination aims to improve objective response rates by targeting multiple oncogenic drivers and overcoming the blood-brain barrier.
- Other names
- selinexor + orelabrutinib + methotrexate + thiotepa + temozolomide-Ruijin Hospital-central nervous system lymphomaSelinexor + Orelabrutinib + MTX/TT/TMZ
02
Targets
DHFR (Dihydrofolate reductase)XPO1 (Exportin-1)DNAGenomic DNA basesBTK (Bruton tyrosine kinase)
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