Dr Dennis Slamon, developer of the breast cancer drug Herceptin, believes the future of cancer rests in more targeted approaches, writes RONAN McGREEVY
EVEN IF he had never discovered the breast cancer drug Herceptin, Dr Dennis Slamon’s rise to the top of his profession would be an inspirational story.
The grandson of Syrian emigrants and the son of a Pennsylvanian coal-miner who was invalided when Slamon was a child, he had none of the advantages of money or access, but qualified by way of scholarship through medical school to become the most famous oncologist in the United States.
The story of Herceptin begins in the 1970s when two American scientists discovered oncogenes, the genes that cause cancer. Oncogenes are mutated versions of normal genes which regulate cell growth.
One such gene was HER2 (human epidermal growth factor receptor 2) which makes the HER2 protein. It was discovered by a microbiologist called Dr Axel Ullrich.
The protein is present on the surface of cells as a receptor which takes signals from the chemical human epidermal growth factor to grow normally. In its mutated form it makes cells grow out of control.
Slamon agreed to test the HER2 gene on the cancer tissue samples he had compiled in his laboratory. He found a match with breast cancer and those samples from women who had an oversupply of HER2 had a particularly aggressive form of the disease.
Working together with the biotechnology company Genentech, he and others discovered an antibody made from mouse protein which stopped the HER2 “overexpressing”, or causing the breast cancer cells to grow out of control. Approximately 20 per cent of breast cancer patients are known as HER2-positive.
Ullrich and Slamon published their findings in Science magazine in 1987, but it would take another 11 years before the Food and Drugs Administration (FDA) in the United States licensed Herceptin for use.
In the intervening years Slamon had to battle the scepticism of the medical profession, the reluctance of Genentech to take on such an unknown treatment when other cancer antibodies had failed, three torturous drug trials, where many patients died, and the attention of desperate women who wanted the drug given to them on compassionate grounds.
If the story of a single-minded obsessive battling numerous obstacles to launch a life-saving drug sounds like the stuff of a Hollywood film, it became precisely that.
Living Proof, based on the book HER2 by Robert Bazell, was released in 2008. Slamon was played by Harry Connick Jr.
Though understandably flattered to be played by such a well-known actor, Slamon says Living Proof is a “Hollywood” version of the truth.
“I had very little to do with the movie. I didn’t co-operate very much, but I do feel good about the positive effects of it and it depicts the patients’ stories very accurately.”
Slamon says the toughest part of all, vividly shown in the movie, was refusing women entry into the trial who did not conform with the FDA standards at the time, but he explains: “If we hadn’t done what we did, the drug would not be available for anyone.”
Herceptin has become one of the great success stories of modern cancer treatments. Taken with chemotherapy, it increases by half the rate of remission and cure for women who are HER2-positive as against chemotherapy alone.
About 400 women in Ireland get the drug every year. Herceptin prevents potentially deadly secondary cancers in many women with early-stage breast cancer. In addition, it cures 5-10 per cent of women with advanced breast cancers which would previously have been incurable. Even those women who are not cured outright can live for years after treatment.
“I don’t know anybody who sleeps at night knowing they have saved as many lives as he has saved,” says Slamon’s friend and scientific collaborator, Dr John Crown
Slamon is coming to Ireland this week to review some of the work being carried out by Crown’s Molecular Therapeutics for Cancer Ireland (MTCI) group which is testing treatments for cancer and the Irish Co-operative Oncology Research Group (ICORG) which is providing patients for clinical trials.
They are looking at therapies for HER2-positive patients who do not respond well to Herceptin and also at those who show the most dramatic improvements.
The story is an ongoing one. The drug is continually being refined and tried with new chemotherapies.
“We can do better,” says Slamon. “There will be more effective ways to block whatever resistance mechanisms have developed in some women. If we are reducing the recurrence rate by half, I want to know what is happening with the other half.”
They are also working on a Herceptin-type treatment for patients with Estrogen Receptor (ER positive) breast cancer. “We hope it will be a HER2-like story,” he says.
It is estimated that the number of women who have taken Herceptin now numbers between a million and two million and approximately a third of those owe their lives to the drug.
“It feels good,” says Slamon with a trademark understatement when asked about the impact the drug has had on cancer sufferers.
“When women tell me about it, it makes all the effort worthwhile,” he explains. “The fact that people didn’t want to believe that this could work was really tough especially when you are correct and people tell you that this can’t be right.”
Slamon believes the future of cancer rests in more targeted approaches which suit the individual patient and addresses the genetic defects which caused them to get cancer in the first place.
“Cancer is not a disease based on the organ and to try to apply a one-size fits-all approach is incorrect,” he says.
“When you look at these patients and you see they have different outcomes, it is because they have different sub-types. I think the whole field is heading in that direction and that’s a good thing.”
Dr Slamon will speak at a meeting on the future of cancer research at the Herbert Park Hotel in Dublin at 7pm this evening. All are welcome. Also see herstory.ie.
