Cetuximab is a monoclonal antibody that is used to treat several cancers including bowel cancer and head and neck cancer.
Also called colorectal cancer, bowel cancer affects the colon and rectum and is one of the most common cancers worldwide. Studies have shown that the epidermal growth factor receptor (EGFR) present on cancer cells is involved in cell signalling pathways that induce abnormal growth, proliferation and spread (metastasis) of cancer as well as the formation of new blood vessels (angiogenesis) in tumors. The receptors activate these pathways when they are bound by EGF.
Cetuximab binds to EFGR to stop the downstream protein signalling that promotes cancer growth. Currently, it is licensed for use as a first-line drug in patients with advanced cancer as well as a second-line drug when patients have failed to respond to other treatments.
However, some of the cancers do not depend on the EFGR signalling pathway for their growth, angiogenesis and spread so it is important to identify the cancers that are dependent on EFGR pathways, to predict whether or not the cancer would respond favourably to cetuximab.
Studies have shown that in the general population, the response rate to cetuximab if used without factoring in EFGR expression status, is around 30%. This proportion rises to over 60% in a population of cancer patients with a cancer that is dependent on EFGR. To understand the predictability of such cancers, certain biomarkers are assessed and some of these include:
One of the proteins involved in the signal pathway that EGFR activates is KRAS 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. In patients with a mutated KRAS gene, drugs such as cetuximab are not effective and only patients with wild type or non-mutated KRAS genes are responsive to the therapy.
Approximately 40% of people with colorectal cancer have a mutated KRAS gene and standard practice now involves testing for these mutations before treatment with cetuximab is initiated.
Other biomarkers that predict if the patient would respond to cetuximab include BRAF and PIK3CA
Reviewed by Sally Robertson, BSc