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sorafenib + topotecan
- Development stage
- Unknown
- Lead developer
- Bayer
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
A combination regimen of the small-molecule multikinase inhibitor sorafenib and the topoisomerase I inhibitor topotecan, investigated primarily in oncology. Sorafenib inhibits serine/threonine kinases RAF (CRAF, BRAF) and multiple receptor tyrosine kinases involved in tumor angiogenesis and proliferation, including VEGFR-1/2/3, PDGFR-β, FLT3, KIT, and RET, thereby exerting antiangiogenic and antiproliferative effects. Topotecan is a camptothecin analog that stabilizes the topoisomerase I–DNA complex, causing replication-induced DNA breaks and apoptosis. The combination has been evaluated in platinum-resistant ovarian cancer (including as combination and maintenance), recurrent/refractory small cell lung cancer, and pediatric refractory/recurrent solid tumors and sarcomas, with dose-limiting hematologic toxicity frequently determining tolerability.
- Other names
- sorafenib plus topotecantopotecan plus sorafenib
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)PDGFRB (Platelet-derived growth factor receptor beta)TOP1 (DNA Topoisomerase I)RAF1 (c-Raf-1 (Y340D/Y341D))VEGFR3 (Vascular endothelial growth factor receptor 3)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)RET (Rearranged during transfection receptor tyrosine kinase)FLT3 (Fms related receptor tyrosine kinase 3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)
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