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doxorubicin + lapatinib
- Development stage
- Unknown
- Lead developer
- GSK
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Doxorubicin + lapatinib is a combination therapy used primarily in the treatment of HER2-positive metastatic breast cancer. Doxorubicin is an anthracycline antibiotic that acts as a cytotoxic agent by intercalating into DNA and inhibiting topoisomerase II activity, leading to DNA strand breaks and apoptosis. It also generates reactive oxygen species that contribute to its antitumor effects[2]. Lapatinib is a small molecule tyrosine kinase inhibitor developed by GlaxoSmithKline (GSK) that targets both epidermal growth factor receptor (EGFR/HER1/ERBB1) and human epidermal growth factor receptor type 2 (HER2/ERBB2), blocking their intracellular phosphorylation domains to prevent downstream signaling involved in tumor cell proliferation[4][6]. The combination has shown efficacy in patients with HER2-positive metastatic breast cancer who have progressed on trastuzumab-based therapies and may be particularly suitable for those at risk of cardiotoxicity or with brain metastases due to its ability to cross the blood-brain barrier[3].
- Brand names
- Caelyx
- Other names
- pegylated liposomal doxorubicin
02
Targets
ABCB1 (P-glycoprotein)ABCG2 (Breast cancer resistance protein)DNAEGFR (Epidermal growth factor receptor)ERBB2 (Erb-b2 receptor tyrosine kinase 2)TOP2A (DNA topoisomerase II)
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