Herceptin 04/02/04. By Richard Twyman Herceptin (also known by its generic name trastuzumab) is a recombinant antibody used to treat advanced breast cancer.

The disease

Breast cancer is the second most common form of cancer in women (after lung cancer) and will affect one in every eight women at sometime during their lives. The disease begins when cells in the breast ducts, or sometimes the breast lobules, start to divide more often than they should. The result is a growth, or tumour, which often can be felt as a lump.

Initially, the tumour is small and remains within a capsule of fibrous tissue. It is described as benign. If caught at this time (stage I), most tumours can be removed by surgery and the disease is often cured. If left untreated, however, tumour cells can spread to lymph nodes (stages II and III) and the disease becomes more difficult to control, with survival rates dropping from over 90 per cent to 50-60 per cent.

Later, the tumour can become malignant, escaping from its capsule and spreading cancerous cells to other parts of the body (stage IV). This is known as metastasis, and at this stage the prognosis is poor.

The target

Many cancers are be caused by DNA amplification, an abnormal situation where a particular DNA sequence is copied over and over again so that the cell may possess hundreds of copies of the same gene. Cells contain many genes that promote cell division, and if such genes are amplified then the cell is likely to divide too frequently, thereby producing a tumour.

In about 30 per cent of breast tumours, there is amplification of a gene called HER2, which encodes a cell surface receptor. The receptor has a binding partner, or ligand, which is outside the cell and fits into the receptor like a key in a lock. The result of receptor-ligand binding is a signal that tells the cell to divide. The abundance of HER2 on the surface of tumour cells causes them to divide very frequently.

The drug and how it works

Herceptin is an antibody drug – a drug based on the structure of the natural antibodies in our bodies that protect us from infection. Such drugs work by binding to and eliminating a particular disease-causing protein in the same way that our natural antibodies bind to and eliminate bacteria and viruses.

Herceptin is thought to inhibit tumour cell growth by binding to HER2 on the surface of tumour cells and causing the receptor to be taken back into the cell, therefore preventing it from transmitting its growth-promoting signal. Like other antibodies, Herceptin may also attract immune system cells that kill abnormal cells, causing the tumour to regress.

Finally, Herceptin is thought to block cellular processes that repair damaged DNA. Therefore, when used in combination with DNA-damaging drugs, Herceptin has yet another way to kill tumour cells.How Herceptin was developed

Herceptin is one of a growing collection of therapeutic antibodies, which are designed to interact with and block the activities of disease-causing proteins in our bodies. The catalyst for the development of Herceptin was the discovery that many metastatic breast cancers carry multiple copies of the HER2 gene, which had previously been shown to cause cancer when introduced into mice.

A breakthrough was made by Dennis Slamon in 1988 when he discovered that the aggressiveness of breast cancer was proportional to the number of extra copies of HER2 in the tumour cells. This led him to approach the biotechnology company Genentech with a proposal to develop an antibody that specifically interfered with the HER2 protein.

Over the next 10 years, a series of antibodies was made and many tests were carried out. Finally, clinical trials in which the best-performing antibody was given to women with metastatic breast cancer showed that the drug was very effective at slowing the progress of the disease.

Herceptin was approved for release in 1998, and has since helped to extend the lives of many women with advanced breast cancer.

Currently, the drug is also being tested to see how effective it is in the treatment of early-stage breast cancer.

Image credit: Darren Hopes