Not only has development of the drug Herceptin saved the lives of an untold number of women with a particularly aggressive form of breast cancer, it also opened new avenues of research that have led to multiple other targeted therapies that attack the disease at its genetic roots. For his pioneering contribution to the creation of Herceptin, UCLA’s Dennis Slamon, MD, PhD, has been awarded the 2019 Lasker- DeBakey Clinical Medical Research Award, widely regarded as America’s top biomedical research honor.
Dr. Slamon, professor and chief of hematology/oncology at the David Geffen School of Medicine at UCLA, shares the award with H. Michael Shepard, an American cancer researcher honored for work he completed at biotechnology company Genentech, and Axel Ullrich, a German cancer researcher from the Max Planck Institute of Biochemistry. The three scientists showed that the monoclonal antibody Herceptin binds to, and destroys, abnormal cells without harming nearby healthy tissue, much like a laser-guided missile hitting a select target. This was a major departure from then-common chemotherapies that Dr. Slamon refers to as the “hand grenade” approach, indiscriminately killing healthy as well as diseased cells.
Proving that antibodies that bind to cancerous cells are an effective method for treating solid tumors transformed cancer care at a time, in the 1980s, when most cancer therapies were focused on excising tumors and developing better chemotherapies. Between 2.7 million and 3 million women have been treated with Herceptin, and women with HER2-positive breast cancer now have among the highest survival rates compared with all women with breast cancer.
“There were a lot of preconceived notions that this approach couldn’t work because prior antibody therapies in cancer had failed,” says Dr. Slamon, who also is director of clinical and translational research at the UCLA Jonsson Comprehensive Cancer Center. “However, we had clear data to back us up, and we really stuck to pursuing it. I grew up being told that I was only limited by my own ability. That always stayed with me. You have to be very careful and critical of your data, but if it looks correct, believe it and chase it despite what others may think.”
The first human clinical trial led by Dr. Slamon was performed at UCLA in 1990. Twenty women — whom he credits as being the real heroes in the story of Herceptin — participated.
“Those women who entered the Phase I trials are not research subjects or patients, they’re colleagues,” Dr. Slamon says. “They’re every bit as much of the story as any of us because they participated in a trial knowing that we might be giving them something that would hurt them. And because it was a safety test, we had to start at levels that were not likely to even help them. But they all agreed and volunteered with the attitude that while it may not directly help them, it might help the next person behind them.”
The Lasker Awards were established in 1942 by Albert and Mary Lasker to recognize researchers, clinical scientists and public servants who have made major advances in the understanding, diagnosis, treatment, cure or prevention of disease, and to raise awareness of the ever-present need for research funding. They are known as the “American Nobel” — eighty-eight Lasker winners have gone on to be awarded Nobels. Dr. Slamon is the second David Geffen School of Medicine scientist to win the award in the past two years; Michael Grunstein, PhD, Distinguished professor Emeritus of biological chemistry, received the Albert Lasker Basic Medical Research Award in 2018 for his groundbreaking research on gene expression.
“Over the course of his 40-year tenure at UCLA, Dr. Slamon has persevered in his research, leading to improved outcomes for patients,” says Johnese Spisso, president of UCLA Health and CEO of the UCLA Hospital System. “His efforts resulted in a new way of understanding breast cancer, and we are grateful for the tremendous impact his work has had on the lives of millions of women worldwide.”
Dr. Slamon and colleagues opened an entirely new area of research. In turn, targeted therapies for cancer, including Erbitux, Sprycel, Nerlynx and Avastin, have emerged, thanks to research by other scientists. Dr. Slamon continues to lead the development of groundbreaking new treatments, such as palbociclib (Ibrance), which was approved by the Food and Drug Administration in February 2015 for women with advanced estrogen receptor-positive, HER-2-negative breast cancer.