Question

The chemotherapeutic monoclonal antibodies and protein kinase inhibitors are considered targeted forms of therapy. How do these two classes of chemotherapeutic agents specifically target cancer? In your answer describe the mechanism of action of Trastuzumab (Herceptin) and Imatinib (Gleevac), two targeted chemotherapeutic agents representing each class. Contrast the targeted mechanisms of action of these drugs to the cytotoxic chemotherapeutic agents.

Answer 1

Molecularly targeted cancer therapies such as protein kinase inhibitors and monoclonal antibodies constitute a rapidly growing and important part of oncology.Unlike conventional chemotherapeutics ,targeted therapies disrupt cancer cells pathogenesis at specific points essential for development and progression of tumor.They disrupt specific targets which helps in minimizing treatment compared to chemotherapy.

AS the type of cancer is not given ,let us take mechanism of action of Trastuzumab towards breast cancer.The family of growth factors comprises of HER1,HER2,HER3 ,HER4 ,these kinases play a critical role in cellular growth and are upregulated in numerous cancers including breast carcinoma.This drug has been proposed to trigger HER2 internalization and degradation through promoting the activity of ubiquitin ligase ,it recruits to the docking site of Tyr and leads to degradation.The major mechnism of Trastuzumab is to attract immune cell to tumor cells that overexpress HER2 by a mechanism called antibody dependent cellular cytotoxicity .Trastuzumab binds to extracellular domain of HER2 can potently suppress cancer cell growths,and survival in bothe direct and indirect manners.Her2 can mutate to cutoff its extracellular domain which inhibits the binding of Trastuzumab to the receptor.This process is called as proteolysis which generates the constitutive kinase activity.