A 61-year-old man arrives at the office after 4 months of easy fatigability, anorexia, and an unintentional weight loss of 4.5 kg (10 lb). His occult blood testing in the stool is positive, and laboratory studies reveal microcytic hypochromic anemia. A 6-cm (2.4-in) mass in the descending colon is discovered during a colonoscopy. Adenocarcinoma is confirmed by biopsy samples obtained during the procedure. A CT scan of the abdomen reveals multiple metastatic liver lesions. Monoclonal antibodies that bind to epidermal growth factor receptors on malignant cells are being considered for treatment. An activating mutation in which of the following will most likely make this therapy ineffective?

Question

Quizplus · Accepted Answer

Eductional Objective: The ligands of the epidermal growth factor receptor (EGFR) stimulate it in a paracrine or autocrine manner, resulting in the downstream activation of KRAS, a membrane-bound GTP-binding protein that stimulates cellular growth and proliferation. Many cancers (for example, colorectal and pancreatic) use this system to drive uncontrolled cellular growth by overexpressing EGFR and its ligands or developing constitutive activating mutations in the KRAS proto-oncogene.
The EGFR signaling system can be targeted for cancer treatment by using monoclonal antibodies (e.g., cetuximab, panitumumab) that block EGFR, resulting in decreased KRAS stimulation and cellular growth. This treatment, however, is only effective in tumors with wild-type (normal) KRAS.

A 61-Year-Old Man Arrives at the Office After 4 Months