In vitro: Pertuzumab significantly inhibits the HRG-α-stimulated cellular growth of the 11_18 cells. Pertuzumab blocks HRG-α-stimulated phosphorylation of HER3, mitogen-activated protein kinase (MAPK), and Akt. In contrast, pertuzumab fails to block epidermal growth factor (EGF)-stimulated phosphorylation of EGF receptor (EGFR) and MAPK. Immunoprecipitation shows that pertuzumab inhibited HRG-α-stimulated HER2/HER3 heterodimer formation. HRG-α-stimulated HER3 phosphorylation is also observed in the PC-9 cells co-overexpressing EGFR, HER2, and HER3, but the cell growth is neither stimulated by HRG-α nor inhibited by pertuzumab. Pertuzumab binds to ErbB2 near the center of domain II, sterically blocking a binding pocket necessary for receptor dimerization and signaling. Pertuzumab is specific for human ErbB2 and does not bind to rodent ErbB2 (neu) with detectable affinity.
In vivo: Pertuzumab has antitumor activity as a single agent in a mouse xenograft model and the combination with trastuzumab strongly reduces EGFR-HER2 signaling and shows significant antitumor activity compared with each monotherapy in NCI-N87, an HER2-positive human gastric cancer xenograft model.
|Cell lines||The lung cells (11_18 cells and Ma-24 cells)|
|Preparation method||The lung cells are exposed to pertuzumab (0.01-100 μg/mL) for 72 h in serum free medium with or without 100 ng/mL of epidermal growth factor (EGF), transforming growth factor (TGF)-α, heparin-binding epidermal growth factor (HB-EGF), orheregulin (HRG)-α. The viability is determined using the MTS assay.|
|Incubation time||72 h|
|Animal models||BALB-nu/nu mice|
|Dosages||20 mg/kg, 40 mg/kg and 80 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation.
Wuerkenbieke D, et al. Arch Gynecol Obstet. 2015 Nov;292(5):1109-16. PMID: 25986891.
Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.
Swain SM, et al. N Engl J Med. 2015 Feb 19;372(8):724-34. PMID: 25693012.
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Cetuximab, a novel molecular-targeted agent,is an inhibitor of EGFR monoclonal humanized antibody interacting with the extracellular binding site of EGFR to block ligand stimulation.
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