On the podium was Professor George Sledge, the chairman of the education committee of the American Society of Clinical Oncology (Asco), widely regarded as the world's leading spokesperson for the science of cancer. He had summoned the delegates to announce that a drug called Herceptin had achieved a dramatic reduction in breast-cancer deaths.
The results were part of an international study called Hera, involving 5,000 women.
The study began in 2001 and is being conducted in 39 countries, including Britain. Herceptin, Sledge said, had achieved a 46% reduction in the risk of recurrence of the early stage of an aggressive breast cancer affecting 25% of women. Recent trials have shown similar results in women with an advanced stage of the condition. He continued: "These are the most stunning results in a clinical trial in my entire professional career." The findings, he went, were "astonishing beyond belief. Biology has spoken, we should listen . . . a new age now begins".
After the figures were read out by the Belgian lead investigator, Dr Martine Piccart, there was a five-minute standing ovation. The significance is indeed stunning. Nearly 10% of women will develop breast cancer during their lifetimes. Each year, more than a million new cases are diagnosed worldwide, with a death rate of nearly 400,000 per year. In Britain, breast cancer is the commonest cancer, though it is rare in men. Over 100 new cases are diagnosed each day. It remains the third commonest cause of cancer death, with around 13,000 victims each year. The Hera result suggests that the lives of 2,800 women could be saved each year by Herceptin.
The Orlando audience, hype-fatigued by years of promises of magic-bullet cures in the pipeline, was powerfully convinced. Each cancer specialist worthy of the name knows that the science behind Herceptin is being applied in laboratories around the world in the hope of transforming treatment not just of breast cancer but also of cancers of the lung, prostate, stomach and ovary, and leukaemia.
The strategy, in scientific terms, is to identify molecular targets for cancer therapy. Herceptin, like another leading cancer drug, Glivec, is designed to activate or deactivate exquisitely complex molecular interactions in the body, creating an entire new group of cancer treatments. Herceptin works by interfering with one of the ways in which cancer cells divide and grow. Glivec, used to treat chronic myeloid leukaemia and a rare stomach cancer, works by blocking signals within cancer cells and preventing a series of chemical reactions that cause the cells to grow and divide. Like Herceptin, it could work for other types of cancer, including cancer of the prostate.
This year's Asco meeting attracted a record 25,000 cancer experts, filling up the hotels of Orlando which normally play host to Disney World tourists. They had jetted in from all parts of the world to meet and greet collaborators who normally correspond by e-mail. Year after year they have been returning to their clinics and laboratories increasingly daunted by the ever-expanding evidence of cancer's hideous complexities. But this year was different.
We were witnessing, I heard more than one delegate say, "a paradigm shift", the phrase first employed by the philosopher Thomas Kuhn to describe how science progresses by long periods of stability punctuated by a revolution, after which nothing is the same again.
Among the optimists was Professor Ian Smith, leader of the British group in the Hera study and head of the breast-cancer unit at the Royal Marsden hospital at Chelsea and Sutton. A cheerful man with a riotous thatch of greying curly hair, he has an inside track on the Hera results. He said that HEGF (human epidermal growth factor) is a protein that occurs naturally in the body. Sometimes it attaches itself to another protein (Her2) on the surface of breast-cancer cells. When this happens it makes the cells divide and grow. Herceptin, developed in the laboratories of the pharmaceutical company Genentech, blocks this process by attaching itself to the Her2 protein so that the epidermal growth factor cannot reach the breast-cancer cells. This stops the cells from dividing and growing. The compound also stimulates the body's own immune cells to help destroy the cancer cells. "What we need to do," says Smith, "are special antibody tests of all breast-cancer patients at diagnosis to determine everyone who could benefit from such treatment."
Behind the Herceptin story are developments in medical science that have been a long time coming. As Dr Charles Sawyers of the Jonsson Comprehensive Cancer Center in LA told a session at Orlando, it had taken 40 years, from the earliest work on a single chromosome (a structure within any cell containing DNA, encoding genetic information inherited from one's parents), to bring compounds like Glivec and Herceptin to the clinic. The intervening years had seen advances in the study of pure biology at the microscopic level in parallel with advances in genetics. The $3 billion human genome project (which identified the sequence of all the genes in the human organism) was completed in 2001. The task of linking these genes to the risk of cancer is ongoing but hugely complex and problematic. Of the 30,000 genes revealed in the project, many are novel with no resemblance to a
gene of known function.
One of the biggest tasks facing biologists is to predict the 3-D structure of the proteins that arise from DNA instructions. It has not been plain sailing. The theory behind antibody therapy, for example, looked straightforward at the outset. Our natural antibodies are the first line of defence against invading antigens or infections. Our immune system is composed of a vast library of these antibodies which are attracted to the invaders: each antibody grasps a specific target while alerting the rest of the system to the nature of the intruder. The idea is to design appropriate antibodies precisely to target antigens produced by tumours, and to inject them into the bloodstream to do battle.
The long progress to new rationalised drugs for cancer, such as Herceptin, Glivec, Erbitux (for colon and rectum) and Ritux (for non-Hodgkin's lymphoma) contrasts dramatically with the way in which chemotherapy was discovered. Chemotherapy, a cytotoxic (meaning that it kills cells), is the traditional treatment of choice to combat the spread of cancer. It was discovered as an unsuspected side effect of mustard-gas weapons on people who happened to be suffering from cancer of the lymph nodes. In some cases, a gas dose, which normally caused blindness and imploding lungs, temporarily destroyed the cancer. It became the basis of variations of chemotherapies that tend to kill cancerous cells, and destroy healthy ones too, while damaging the immune system in the process. The side effects are the fear of all cancer sufferers: nausea, hair loss, skin afflictions.
