Conventional cancer therapy makes use of what are known as cytotoxic (“cell killing”) agents. While their specific mechanism of action varies, they work by killing all growing and dividing cells in the body. Since tumor cells grow much faster than normal cells, the rationale is that conventional therapy will kill the tumor cells before normal cells will be damaged. However, as some normal tissues also grow very rapidly, e.g. the lining of the stomach and gut, bone marrow, ovaries, testes, hair follicles, etc, cytotoxic therapy has significant side effects.

A superior solution would be specifically to target and destroy tumor cells while leaving normal cells untouched. To be able to do this, a specific marker identifying a cell as cancerous is required, together with a means of targeting this marker and subsequently destroying the cell.

Epidermal growth factor receptor (EGFR) is commonly highly expressed or over-active in many tumor types. Its main function, normally tightly controlled, is to promote the growth and division of cells, the repair of cellular damage and the movement of cells within surrounding tissue. In tumors, EGFR’s effects are enhanced. This leads to the growth of tumors, increased resistance to chemotherapy or radiotherapy, and the formation of metastases (small pieces of tumor which break off and invade other parts of the body).

There is therefore a rationale for targeting cells which have EGFR on their surface, and early laboratory research demonstrated that blocking the activity of this receptor had a potent anti-cancer effect.

Cetuximab is a monoclonal antibody which, like the antibodies circulating as part of your own immune system, specifically targets and locks on to a particular target – in this case, EGFR. Cetuximab works in several ways:

• It attaches itself directly to EGFR and prevents it from becoming active.
• EGFR with cetuximab attached is drawn inside the cell and destroyed, thereby reducing the amount of EGFR on the cell surface which could be activated.
• Since it is an antibody, cetuximab has the ability to bring tumor cells to the attention of the immune system, which can then kill them.

Cetuximab is the first EGFR-targeting drug approved for use in bowel cancer. As cetuximab targets cancer cells specifically, it does not have the side effects usually associated with standard cytotoxic drugs used in this disease.

Through the development of cetuximab, Merck KGaA is providing further treatment options for patients with advanced bowel cancer, and is continuing to develop new and effective cancer treatments.