Biology meets industry – genomics, proteomics, phenomics
Box 2 | Case study – Remicade and Glivec
Glivec is a molecularly targeted drug treatment for chronic myeloid leukemia (CML), manufactured by the pharmaceutical company Novartis. It operates by blocking the specific signal transduction pathway that is abnormally activated in leukemic cells. Blocking the pathway prevents the uncontrolled proliferation of white blood cells that characterises the deadly cancer. A primary difference between Glivec and more conventional forms of cancer treatment such as radiotherapy and chemotherapy is that Glivec specifically targets the defective pathway which causes the disease. Radiotherapy and chemotherapy are toxic to all the body's tissues, but are effective cancer treatments because fast-dividing cancer cells are more susceptible than normal healthy cells. However, the toxicity to healthy cells results in serious side-effects for the patient.
Research into a targeted treatment for the cancer was made possible when researchers at the California Institute of Technology in the 1980s discovered that a single defective protein (a tyrosine kinase enzyme) could cause CML – this made it a potential candidate for a targeted treatment. By the mid-to-late 1990s, researchers had developed from a promising but weak-acting inhibitor class of molecules a powerful, specific inhibitor that could inhibit the abnormal cell pathway. Glivec has proven to be a very effective treatment for the disease, and trials are underway to determine its effectiveness against other forms of cancer.
A primary drawback to the treatment is its cost – a year's treatment with Glivec costs around $50,000. The drug is listed under the Commonwealth Government Pharmaceutical Benefits Scheme in Australia, making it affordable for sufferers. It was first approved for subsidy in 2001 for some patients with CML. Coverage has since been expanded, and Glivec is now subsidised as a first-line treatment against the early, chronic stages of CML.
Remicade is a drug designed to treat certain autoimmune diseases, especially rheumatoid arthritis and Crohn's disease. It uses monoclonal antibody technology to produce a specific antibody (patented by Australian biotech company Peptech). The antibody blocks the action of the protein Tumour Necrosis Factor Alpha (TNF-α). TNF-α is a powerful regulator of the body's inflammatory immune response which is overproduced in sufferers of rheumatoid arthritis and other auto-immune diseases. Remicade was registered in Australia in August 2000, but was denied listing on the PBS until November 2003. While slightly less expensive than Glivec (at $20,000 per year) there are more sufferers, and the total cost to the PBS is higher. The delay in approving subsidy of the drug is illustrative of the difficult decisions government bodies will have to make about these new technologies – especially in weighing up expensive treatments that, while not life-saving, can have a tremendous impact on a patient's quality of life.
Box
Box 1. Unveiling the proteome
Related site
Glivec
(Imatinib) (transcript of The Health Report, 21 July 2003,
Australian Broadcasting Corporation)
Posted July 2004.