Question

The primary way that EGFR increases expression of cyclin D involves acti- vating a protein called Ras. In colon cancer, genetic testing is often used to see if patients have wild-type Ras (which acts as a switch and is turned on or off by signals from inside and outside the cell) or mutant Ras (which is always turned on because the part of it that helps it turn off is broken). In a colon cancer patient with mutant Ras, would you expect cetuximab to be an effective therapy? Why or why not?

Answer 1

Yes , Cetuximab is an effective therapy to treat metastatic colon cancer. The drug cetuximab is man made monoclonal antibody and   is an inhibitor of epidermal growth factor receptor (EGFR). The EGFR is present in both normal cells as well as mutated cells which serves as a receiver for receiving signals and plays and essential role in cell division. But large amount of any growth receptor leads to excessive cell division and growth.

Cetuximab binds firmly to EGFR which acts as the receiver hence either deactivating or degrading them. A protein called KRAS (a part of RAS-MAPK signalling pathway) which sends signal from EGFR to other proteins of the cell. A small G-protein is encode by KRAS gene.Mutations in KRAS makes cetuximab resistant in these patients. Thus KRAS mutational analysis can help in detecting if the patient will respond to the drug or not.