Trastuzumab: Difference between revisions
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[[Epidermal Growth Factor Receptor|Human Epidermal Growth Factor Receptor 2]] (HER2) is overexpressed in approximately 30% of breast [[Cancer|cancers]]. Upon receiving a mitogenic signal, HER2, located in the cell membrane, dimerizes and transfers signals to receptors within the cell. This activates different pathways including the [[PI3K]] pathway and MAPK pathway, promoting cellular survival and replication. Trastuzumab is a humanized [[monoclonal antibody]] <scene name='Trastuzumab/Trastuzumab_h/1'>that binds to the domain IV</scene> of the extracellular segment of the HER2 receptor. It has been suggested that Trastuzumab binding disrupts receptor dimerization, preventing the errant signal from being transfered. This ultimately causes cells to arrest druing the G1 phase of the cell cycle, halting cellular proliferation.<ref>PMID:14528282</ref> <scene name='Trastuzumab/Vouns/5'>The extremely precise binding interaction</scene> between the Trastuzumab [[antibody]] Fab and HER2 involves residues Arg 58, Arg 50, Tyr 33, Tyr 100, & Gly 99 on the heavy chain Fab, Thr 94, His 91, Tyr 92, Tyr 32, & Tyr 53 on the light chain Fab, and Glu 558, Gln 561, Asp 560, Phe 573, Lys 569, Pro 572, Pro 571, Lys 593, Cys 601, Cys 604 & Gln 602 on the HER2 polypeptide. | [[Epidermal Growth Factor Receptor|Human Epidermal Growth Factor Receptor 2]] (HER2) is overexpressed in approximately 30% of breast [[Cancer|cancers]]. Upon receiving a mitogenic signal, HER2, located in the cell membrane, dimerizes and transfers signals to receptors within the cell. This activates different pathways including the [[PI3K]] pathway and MAPK pathway, promoting cellular survival and replication. Trastuzumab is a humanized [[monoclonal antibody]] <scene name='Trastuzumab/Trastuzumab_h/1'>that binds to the domain IV</scene> of the extracellular segment of the HER2 receptor. It has been suggested that Trastuzumab binding disrupts receptor dimerization, preventing the errant signal from being transfered. This ultimately causes cells to arrest druing the G1 phase of the cell cycle, halting cellular proliferation.<ref>PMID:14528282</ref> <scene name='Trastuzumab/Vouns/5'>The extremely precise binding interaction</scene> between the Trastuzumab [[antibody]] Fab and HER2 involves residues Arg 58, Arg 50, Tyr 33, Tyr 100, & Gly 99 on the heavy chain Fab, Thr 94, His 91, Tyr 92, Tyr 32, & Tyr 53 on the light chain Fab, and Glu 558, Gln 561, Asp 560, Phe 573, Lys 569, Pro 572, Pro 571, Lys 593, Cys 601, Cys 604 & Gln 602 on the HER2 polypeptide. | ||
'''SEE ALSO:''' [[Journal:Acta_Cryst_D:S2059798319006995|Structural insight into a matured humanized monoclonal antibody HuA21 against HER2-overexpressing cancer cells]]<ref>doi 10.1107/S2059798319006995</ref> | |||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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