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vandetanib + pegylated liposomal doxorubicin
- Development stage
- Unknown
- Lead developer
- AstraZeneca
- Modality
- Nanoparticles → Drug Delivery Systems, Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination comprises **vandetanib** (an orally administered small molecule tyrosine kinase inhibitor of VEGFR, EGFR, and RET pathways) and **pegylated liposomal doxorubicin** (an anthracycline chemotherapeutic encapsulated in pegylated liposomes for enhanced tumor delivery and prolonged circulation). Vandetanib disrupts angiogenesis and tumor proliferation by blocking vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET signaling. Pegylated liposomal doxorubicin inhibits DNA replication by intercalating into DNA and inhibiting topoisomerase II; its pegylated liposome formulation increases tumor deposition and decreases exposure to healthy tissues, reducing some toxicities. The combination is under investigation for recurrent platinum-resistant or refractory ovarian cancer; feasibility was shown, but with notable toxicity requiring dose adjustments or cessation in a subset of patients[1][2][4][6].
- Brand names
- Doxil
- Other names
- ZD6474ZD-6474ZD 6474PLDLipoDox
02
Targets
EGFR T790M (Epidermal growth factor receptor T790M mutant)TOP2A (DNA topoisomerase II)TOP1 (DNA Topoisomerase I)DNASRC (Proto-oncogene tyrosine-protein kinase Src)VEGFR3 (Vascular endothelial growth factor receptor 3)VEGFR2 (Vascular endothelial growth factor receptor 2)RET (Rearranged during transfection receptor tyrosine kinase)
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