Under the Microscope: Last week I described cancer and briefly summarised the history of its treatment up to the development of chemotherapy in the mid-20th century. This week I will describe some of the latest approaches to cancer treatment, concentrating in particular on one treatment based on choking off the blood supply to tumours, writes Prof William Reville
In the early 20th century, the only cancers that could be cured were small tumours localised enough to be completely removed by surgery. If some very small tumours evaded removal it was possible to subsequently treat them with radiation. If tumour growth had spread beyond the reach of surgery and radiotherapy it could be tackled by chemotherapy. Using chemotherapy after surgery to kill any remaining cancer cells in the body is called adjuvant therapy.
There have been very significant modern developments in chemotherapy. New drugs have been developed and are often used in combination for greater effectiveness. Several cancers can now be successfully treated, including acute childhood leukaemia, testicular cancer, and Hodgkin's disease. Many other cancers can be controlled for long periods.
Unfortunately cancer remains a big problem. It is the second most common cause of death in Ireland. From 1994 to 2001, 49,604 new cancers were diagnosed in women in Ireland, and 52,954 cancers were diagnosed in men. Over this same period 27,788 women and 32,030 men died from cancer. The top three most frequent cancers in women (the figures in parentheses are percentage relative frequencies) are: breast (27.8 per cent), colorectal (bowel) (12.8 per cent) and lung (9.1 per cent). The statistics for men are: prostate (20.7 per cent), colorectal (15.5 per cent) and lung (15.3 per cent).
Cancer is mainly a disease of older people. Life expectancy in Ireland is increasing and therefore the number of people afflicted with cancer is expected to rise in the coming years.
The goal of cancer treatment is either to kill the unruly cancer cells or to stop them growing. The second half of the 20th century saw an explosion in our knowledge of how the cell works at the molecular level. This knowledge is now being used to treat cancer. Indeed, our only hope of defeating cancer, such a wily adversary, on the broad front is through application of this knowledge. This is a powerful example of why we must always support basic research that produces new knowledge.
Methods of efficiently targeting tumours have been developed. One such method is called monoclonal antibody therapy, where antibodies, specially produced in the laboratory and capable of recognising sites on the surface of cancer cells, are injected into the body. These antibodies bind to cancer cells and either inhibit their further growth or mark them out for destruction by the body's own immune system. New approaches are also being developed where the monoclonal antibodies are tagged with chemotherapeutic agents.
New approaches based on molecular knowledge of the cell are now being used to tackle cancer, for example signal transduction, genetic therapy and anti-angiogenesis. Signal transduction is the complex process whereby growth signals are transmitted to the genetic headquarters of the cell (the nucleus). The aim is to interfere with this process in cancer cells and success has been achieved in treating one chronic form of leukaemia. Genetic therapy aims to target specific genetic characteristics of cancer cells.
The growth of new blood vessels is called angiogenesis. This is a normal process essential for embryonic development, human growth and wound repair. During angiogenesis a protein is secreted called Vascular Endothelial Growth Factor (VEGF) that stimulates the growth, survival and repair of blood vessels. In order for a tumour to grow it must develop its own blood supply. VEGF is produced in super-abundance around a tumour, encouraging it to develop and grow. The new blood vessels that support the tumour are immature and leaky and this impedes the delivery of chemotherapy to treat the tumour.
The new cancer treatment approach of anti-angiogenesis disrupts the formation of new blood supply in the tumour. A new drug called Avastin, developed by Hoffman-La Roche Ltd, shows great promise. Avastin is a monoclonal antibody delivered by infusion during chemotherapy. Avastin inhibits the production of VEGF around the tumour, inhibiting the development of the tumour's immature blood supply and enhancing the effectiveness of the chemotherapy.
The good news is that Avastin in combination with conventional chemotherapy is the first anti-angiogenic agent which consistently-demonstrated survival benefit in the three most common tumour types, colorectal cancer, breast cancer and lung cancer (eg report in New England Journal of Medicine 2004, Vol 350, pp 2335-2342 by H Hurwitz and others). Trials have also shown that Avastin/chemotherapy treatment of patients with previously untreated advanced breast cancer doubled the length they survived compared to patients treated with chemotherapy alone. Avastin is now being tested for effectiveness against other types of cancer. This approach could well become the backbone of cancer treatment.
The results of a large Roche-sponsored survey of 500 cancer specialists and patients across the EU show that 40 per cent of patients were not sure of what treatment they were currently receiving and felt completely uninformed about technological advances that might help them overcome cancer. This gap in knowledge causes concern for both patient groups and physicians.
When Richard Nixon announced a war on cancer in 1970, he never envisaged the conflict would be so protracted.
William Reville is associate professor of biochemistry and public awareness of science officer at UCC - http://understandingscience.ucc.ie