Breast Cancer - Role of Animals

There is a wide range of breast cancer treatments. They include using hormones to stop the growth of cancerous cells, high dose x-rays and chemotherapy to kill cancer cells, and surgery. The latest option is immune therapy which boosts the body's own disease-fighting system. All of these treatments were developed using animals.

Two key ways in which animal experiments play a part are trying to understand what leads to cancer in the first place and testing out new treatments before they are given to patients.

Early events
Breast cancer is not normally diagnosed until a lump has formed. But this is too late - the events that caused the cancer to begin have already taken place. Doctors and scientists need to be able to see the early days of cancer, and to do this they tend to use rats or mice.

Rodents and humans share many features of normal and cancerous growths. However, the animals have a shorter life span, and their tumours progress rapidly - a life-threatening (malignant) tumour is observable within 6-18 months. In humans, cancer can take years to develop. Thus using rodents is the quickest route for finding potential new treatments.

What usually causes a cell to become cancerous is damage to its DNA. Such damage can lead to out-of-control cell growth, and eventually a tumour. Cancerous tissue from these rats and mice can be grown in culture to determine which genes were disrupted by the cancer-causing substance.

Not all animal work needs to be carried out in mammals. The cells of simple yeasts, for example, grow and divide in the same way as human ones. Oddly-shaped yeast cells are a sign that genes involved in growth are misbehaving. These same genes may also be involved in cancer. Once identified in yeast, it is much easier to locate the corresponding human gene. Sir Paul Nurse, a British scientist, was one of three who received the 2001 Nobel prize for research in this area.

Humans have a role to play too. Breast cancer tissue obtained by biopsies or mastectomies is compared with normal tissue. This helps scientists to identify genes that have gone haywire. What those genes are meant to be doing can then be studied in animals, such as worms, zebra fish, and rodents. Understanding gene function helps identify possible targets for new medicines.

While yeast cells all look the same, in more sophisticated animals, even the tiny C. elegans worm, there are different cells for different functions e.g. muscle and nerve cells. Growth of specialised tissue is controlled by pathways of genes that only function during certain periods of development such as adolescence. Knowledge of how development goes awry is particularly useful for understanding childhood cancers.

Medicines
A number of different animal models are used to evaluate new cancer medicines.

Carcinogen exposed animals
To test for cancer-prevention properties, scientists will often use carcinogen-treated rats. These are rats that have developed cancer after exposure to a cancer-causing source. Tamoxifen is perhaps the best known example of this approach. It blocks the actions of the hormone oestrogen and lowers the chance of the breast cancer returning.

Xenograft models
The anti-tumour activity of drugs such as doxorubicin and epirubicin was observed using xenograft studies. With xenografts, human cancer cells are transplanted into animals, so that their cancers become more like ours. Xenograft studies are easy to conduct and relatively rapid, however they have their limitations. They cannot test immune-based therapies because the tumour tissue is foreign and would be rejected. Nor can they be used to evaluate cancer prevention, as the starting point is already cancerous.

Genetically modified animals
Here mice have specific genes altered to match the changes seen in human breast cancer. This is feasible because mice have counterparts for 99% of our genes. Genetically modified mice are brought closer to the situation with patients because, unlike xenografts, they start with a DNA mutation, rather than a cancerous cell. Thus events following from a DNA change to tumour growth can be studied, and new targets for medicines revealed.

Zebra fish develop a wide variety of cancers and it is now possible to create transgenic lines. The small size of zebra fish, their development outside the mother, and the fact they are almost see-through allows observation not possible with mammals. Cancer is genetically complex, but since zebra fish produce hundreds of offspring a week, the capacity for identifying novel targets for more efficient anti-cancer drugs and therapies is much greater than in mammals.

Gene knockout animals are missing one or more genes. These models have been very successful in the search for drugs to prevent cancer because they mimic cancers in people that have non-functioning (as opposed to misfunctioning) genes. Using these mice, derivatives of vitamin A (retinoids) were found to suppress the development of an invasive cancer that does not contain oestrogen receptors (and is less likely to respond to hormonal treatments such as Tamoxifen). Retinoids are now being tested on people in clinical trials.

Immune-based therapy
The immune system's job is to recognise and destroy foreign substances (such as viruses and bacteria). The same processes for fighting off flu or a cold may apply to cancer. The aim is to persuade the immune system to mark tumour cells for destruction. Testing in mice has been successful, and has led to the immune treatment herceptin, which slows down or even stops the growth of breast cancer.

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