Developer of a Lifesaving Monoclonal Antibody for Women, Herceptin: Dr. Dennis J. Slamon

Breast cancer is a condition in which the cells of the breast proliferate uncontrollably. There are several types of breast cancer. The kind of breast cancer is determined by which cells in the breast develop into cancer. Women with human epidermal growth factor receptor 2 (HER2)–positive breast cancer had a poor prognosis in the early 1990s, living an average of 3 to 5 years following diagnosis. That changed in 1998, with the development of Dr. Dennis J. Slamon’s monoclonal antibody treatment Herceptin. The breakthrough medication has been used to treat between 2.7 million and 3 million women, and women with HER2-positive breast cancer currently have among the greatest survival rates of all women with breast cancer.

Dr. Dennis J. Slamon, MD (FEL ’82), Ph.D., of UCLA, is the 2019 laureate of the Lasker-DeBakey Clinical Medical Research Award, widely considered as America’s greatest biomedical research prize. Before Dr. Slamon’s parents relocated to New Castle, West Virginia, his father, uncle, and grandpa were all coal miners.

He was often exposed to the physicians who treated him and his family as a youngster growing up in New Castle. After surviving two mine cave-ins, his father Joseph had abandoned coal mining, only to lose his leg in a terrible automobile accident. As a result, house calls by doctors were not uncommon at the family’s home.

That early notion remained as Dr. Slamon grew up in a community where education was not valued and sons typically followed their dads into the mills or mines. That, however, would not be Dr. Slamon’s route. So Dr. Slamon concentrated on his studies, and he excelled. “If anything piqued my attention, I’d immerse myself into it,” he adds. It is a characteristic that is still present today. In high school, he acquired a strong interest in biology and began to ponder his two passions — medicine and biology — and how to combine the two.

It was a scholarship to Washington and Jefferson College, a tiny liberal arts college in neighboring Washington, Pennsylvania, from there. Dr. Slamon was the first person in his family to attend college. He worked at a steel factory over the summers to help pay for his schooling. Following graduation, he considered scholarship offers from West Virginia University, the University of Pittsburgh, and the University of Chicago.

Dr. Dennis J. Slamon got his Ph.D. in cell biology the same year he graduated with honors from the University of Chicago’s Pritzker School of Medicine in 1975. He finished his internship and residency at the University of Chicago Hospitals and Clinics, where he rose to the position of chief resident in 1978. He became a fellow in the Division of Hematology/Oncology at UCLA a year later.

Dr. Slamon got right to work, starting his “marriage” of research and patient care. He got interested in oncogenes, a newly discovered class of genes. When oncogenes are healthy, they are “growth-regulating” genes involved in normal cell growth. When mutations occur, however, they can cause a cell to expand out of control, resulting in cancer. With the help of UCLA’s Jonsson Cancer Center Foundation and UCLA, he began to create a bank of human tumors from physicians who had excised them from patients for therapeutic purposes (lung, colon, liver, and breast). Dr. Slamon’s collection was gruesome, but he thought that understanding the molecular composition of a tumor was critical to understanding cancer’s origins.

Dr. Slamon hired a UCLA student, Wendy Levin, and showed her how to identify matches between oncogenes and tumors at this early stage of his work. It was laborious work, breaking up a sample of tumor tissue that had been frozen in liquid nitrogen, extracting the DNA, and looking at one gene at a time for anomalies. But her efforts paid off on a Saturday afternoon in June 1986, when she discovered a link between the HER2 gene and a breast cancer tumor. She rang Dr. Slamon at home, offering to drive out to his house to show him the results. Dr. Slamon decided to postpone the procedure until Monday.

Dr. Slamon started evaluating monoclonal antibodies from several biotech businesses and university laboratories. Dr. Slamon tested a monoclonal antibody produced at Genentech on cancer cells cultured in a petri dish while working with Dr. Ullrich. It was yet another epiphany. When HER2 breast cancer cells were treated with the monoclonal antibody, the malignant cells ceased growing and dividing. When the researchers withdrew the antibody, cancer regrew. Moreover, the antibody did not affect the other cells in the plate. Herceptin was that antibody.

In the early 1990s, women with the HER2+ subtype had a three-to-five-year life expectancy following diagnosis. Women with HER2+ breast cancer currently enjoy one of the best prognoses of any kind of breast cancer. According to Dr. Slamon’s studies, Herceptin boosts the length of time patients survive following their diagnosis by more than half. Women with the HER2+ subtype now have an average of seven to ten years of disease-free life, depending on the stage of diagnosis. The medication has been used to treat an estimated 2.7 million to 3 million women worldwide.

Dr. Slamon and his colleagues spent over 12 years doing laboratory and clinical research that resulted in the creation of the novel breast cancer medication Herceptin, which targets a specific genetic mutation seen in around 25% of breast cancer patients. To recognize Dr. Slamon’s achievements, President Clinton named him to the three-member President’s Cancer Panel in June 2000.

He and his team have received many national research prizes in recognition of his scientific achievements. Dr. Slamon received the Lasker-DeBakey Clinical Medical Research Award in 2019 for the pioneering discovery of Herceptin. Dr. Slamon and colleagues H. Michael Shepard and Axel Ullrich were recognized by the Albert and Mary Lasker Foundation for demonstrating that monoclonal antibodies were a viable and effective strategy for treating solid tumors, paving the way for the development and deployment of antibodies to treat cancer.

Dr. Slamon, professor and chief of hematology/oncology at UCLA’s David Geffen School of Medicine, is credited with the ground-breaking development of the breast cancer drug Herceptin, a lifesaving monoclonal antibody for women with HER2-positive breast cancer, a particularly aggressive form of the disease. Monoclonal antibodies are lab-created proteins that, when injected into people, attach to and kill particular invading species such as cancer cells.

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