His single-minded determination to cure cancer led to a battle for research funding and the eventual development of a revolutionary breast cancer treatment. Sandra Ryan speaks to leading American oncologist Professor Dennis Slamon
One of US President Barack Obama's more over-ambitious presidential goals, perhaps, was his assertion last year that he hopes to “conquer cancer in our time”. One of the world's leading cancer specialists isn't sure he'd use the word "cure."
"The idea of [calling for] a cure does scare me a little bit because I don't think that's realistic in some cancers, at least not yet," Professor Dennis Slamon, director of UCLA’s division of haematology/oncology, told IMN. "But I like the general overall idea, and I'm thrilled about the focus on health. It will happen eventually."
It is understandable that Prof Slamon-- in Dublin recently for a special event at the Royal College of Physicians in Ireland (RCPI) to discuss his ground-breaking breast cancer research-- sees a cure for cancer as possible.
In the 1970s, while earning his PhD in cell biology and completing his internship and residency at the University of Chicago Hospitals and Clinics, he spent much of his time frustrated; watching chemotherapy and radiation help some breast cancer patients and devastate others. Among the grimmest prognoses at the time were those of the nearly one in four women—45,000 in the U.S. and 250,000 worldwide annually—whose tumours tested positive for the Human Epidermal Growth Factor Receptor 2 (HER2). The presence of HER2 often meant recurrence or death just two or three years after receiving the best available therapies. He and his colleagues watched women die repeatedly; women who now live long after their disease enters remission. This frustration would eventually change the course of breast cancer.
Prof Slamon and his research team became what he refers to as “gene profilers”, investigating and proving the role HER2 plays in this type of cancer. Experiments with humanised mouse-antibodies eventually revealed a combination that blocked the protein, halting HER-2–positive breast cancer in its tracks.
That combination, ultimately named Herceptin, significantly improved disease-free survival rates when combined with chemotherapy. But the trek from theory to treatment took 12 grueling years. The promising findings uncovered by Prof Slamon and his team were not enough to convince Genentech, who owned the research, to continue funding the work.
Fortunately, friends like American anti-cancer activist Lilly Tartikoff and Lisa C. Paulson of the US Entertainment Industry Foundation raised tens of millions for his work after seeing the potential effect of the research (“money is to cancer research as oxygen is to breathing”, Prof Slamon remarked). He reached his goal in November 2006, when Herceptin became one of the first molecularly targeted therapies for use in early stage, HER2-positive breast cancer ever approved by the Food and Drug Administration.
“The drug’s release changed HER-2–positive breast-cancer patients from having among the worst outcomes to having among the best—in some cases a combination of the drug and chemotherapy actually cures the patient,” Prof Slamon explained.
Herceptin works synergistically with other chemotherapy treatments, increasing disease-free survival time by 50 percent.
Prof Slamon, who is also director of the Revlon/UCLA Women’s Cancer Research Programme at the Jonsson Comprehensive Cancer Centre in LA (A Revlon charity also funded some of this research in the ‘90s), has won more than a dozen major national and international awards for his work. The story of developing Herceptin was made into a Lifetime network film in 2008 (Dr Slamon was played by Harry Connick, Jr.). The film tells the story of how, after the drug company withdraws its money from the project, Prof Slamon has to act fast to raise funds for the trials needed for approval.
"It's a story that people may be interested in," said Prof Slamon, "but the real heroes of this story are all the women who enrolled in the original clinical studies without knowing whether or not this drug would help them. They deserve all the credit."
He praised Ireland’s oncologists for getting involved in targeted therapy trials early on, particularly Professors John Crown and Ken O’Byrne. Prof Slamon has begun a collaboration with Prof Crown at the Cancer Clinical Research Trust.
In June of this year, Dr Slamon found that Herceptin also shows promise in treating HER2–amplified gastric cancer—approximately 20 per cent of all cases.
“In addition to looking for more effective diagnosis and treatment options for ovarian and other breast cancers, we are also conducting clinical trials of a HER2–positive ovarian-cancer treatment and also training six teams of UCLA researchers to use the same mutation-targeting tactics to find treatments for lung, colorectal and pancreatic cancers; sarcomas; and melanomas,” Dr Slamon revealed.
The only blip on the radar is the huge cost of these therapies. But personalised treatment has to be the future of cancer care, he said.
“Targeted therapies are the present and future. A ‘one size fits all’ approach may be cheaper but it is not the best option and actually works out less cost effective in the long run. We have to treat patients in different ways based on molecular sub-types, and have to basically find the HER2-like gene that is going to change treatment.”
Awareness of breast cancer internationally is high (it even has its own colour); by contrast, lung cancer—the disease with the worst prognosis and cure rates—is not as well known or discussed.
Some have even asked why breast cancer gets so much attention, often at the expense of other prominent cancers. It has been suggested that breast cancer is perceived (by the media and the public) as a more sympathetic, “softer” disease; lung cancer, on the other hand, has connotations of smoking and the lingering belief that patients may bring it on themselves.
Dr Slamon disagrees with this attitude--- he said it is not about having “the biggest piece of the pie, but about needing a bigger pie”.
“Advocacy is the issue here. In the 1970s and 80s breast cancer was a prevalent disease but not much was done about it—it had a small slice of the funding allocated for research and it wasn’t spoken about much. Patient advocacy groups turned breast cancer into a political issue, had rallies and meetings, raised awareness among women and did brilliant, necessary work. For lung cancer, yes it is a different issue; the advocacy is not quite at the same level.”
Lung cancer is also a major focus of targeted therapy research. The difference is, said Dr Slamon, they don’t fully know yet what targeted therapy can achieve for these patients and what combination is best.
“Also, the group that can benefit from drugs like Tarceva—because of Epidermal Growth Factor Mutations (EGFR)—is much smaller than the HER2-positive breast cancer group. We don’t know yet what will happen in lung cancer, whether it will be Tarceva plus another drug that will eventually improve disease outlook. Metastatic breast cancer used to be incurable. The potential is there. We’re lucky because the day is finally here where the science exists to create targeted, less toxic therapies as an alternative to throwing in a hand grenade and hoping to kill more bad cells than good."
