The Her-2 gene encodes a glycoprotein that is a member of the family of Epiderma
ID: 227398 • Letter: T
Question
The Her-2 gene encodes a glycoprotein that is a member of the family of Epidermal growth factor (EGF) receptor tyrosine kinases. Her-2 gene amplification is detected in up to 30% of breast cancers. Breast cancer patients that show the amplification of the Her-2 gene can be effectively treated with Herceptin, a monoclonal antibody that specifically binds to and prevents the dimerization of Her2 receptors. Based on your knowledge of immunology, each Herceptin monoclonal antibody can potentially bind to how many Her-2 receptor molecules and why? Propose an alternative target in the Her-2 signaling pathway that may be effective in treating this type of cancer and explain why it could be effective.Explanation / Answer
Answer a- Since Herceptin is a monoclonal antibody, it has a monovalent affinity i.e it binds to the same epitope of theHER2 receptor. Hence each molecule of Herceptin can bind to only one HER2 receptor at a time, thereby preventing the dimerization.
Answer b- The other targets could be-
The intracellular domain (tyrosine kinase) is another target in the HER2 signaling pathway. There are molecules which prevent the phosphorylation of tyrosine kinase. An example is lapatinib, molecular inhibitor of HER2 and HER1 tyrosine kinase domain. It is a safe and orally effective drug for the treatment of HER1 or/and HER2 overexpressing breast cancer cells.
Instead of targeting the 3 domains of the HER2 receptor, the gene expression of HER2 can be directly inhibited by oligonucleotides including antisense oligonucleotide and siRNA. Antisense oligonucleotide binds to the complementary mRNA sequence, leading to its degradation by endogenous nuclease RNase H. The resultant downregulation of HER2 mRNA causes inhibition of HER2 overexpressing cancer cells
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