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Cetuximab Uses

By Dr Ananya Mandal, MD

Cetuximab is a monoclonal antibody that specifically inhibits the epidermal growth factor receptor (EGFR).

EGFR is a transmembrane glycoprotein that is a member of the ErbB family of receptors which is one of four groups making up the receptor tyrosine kinases. The other three subfamilies of the ErbB family are HER2, HER3, and HER4.

When EGFR binds to EGF, the receptor undergoes dimerization which leads to the phosphorylation of tyrosine. This, in turn, elicits downstream signalling proteins involved in signal transduction pathways that lead to DNA synthesis and cell proliferation.

EGFR signalling also decreases apoptosis and increases the motility of tumor cells as well as playing a role in angiogenesis or the formation of new blood vessels. EGFR is expressed in various different human cancers and inhibitors of EGFR can be used to block the signalling pathways that induce tumor cell proliferation and survival.

Cetuximab binds to EGFR and inhibits the cascade of activity EGFR would usually induce. The phosphorylation and activation of receptor-associated kinases is stopped, which prevents cell growth and induces apoptosis.

One of the proteins involved in the signal pathway that EGFR activates is KASR but if this protein is mutated, it may send a signal to the cell to divide uncontrollably even when EGFR has been blocked by cetuximab. Therefore, standard practice involves testing for KRAS mutation before cetuximab is treatment is initiated.

Some of the uses of Cetuximab include:

Colorectal cancer
Cetuximab is approved for the treatment of bowel cancer in patients who express "wild type" KRAS or KRAS that is not mutated. Patients who have failed to respond to oxaliplatin or irinotecan based therapy are usually responsive to cetuximab.

Metastatic colorectal cancer
Cetuximab is useful in patients with metastatic colorectal cancer with the wild type KRAS gene.

Head and neck cancer
Cetuximab is also approved for the treatment of head or neck squamous cell cancer.

The drug is usually administered during a 120 minute infusion at a dose of 400 mg per square meter of body surface area. After this initial dose, a weekly, 1- hour infusion is given at a dose of 250 mg per square metre of body surface area.

Reviewed by , BSc

Further Reading

Last Updated: Jan 14, 2014

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