Dennis J. Slamon, MD, PhD
The idea that one kind of cancer may include several subtypes, each marked by unique mutations that can be targeted with tailor-made therapies, is taken for granted these days.
Much of today’s research is focused on identifying hallmarks of cancer subtypes and developing medications to target them, and more than 65 targeted therapies for various cancer types are on the market in the United States.
Follow that trend back to its beginning and you’ll find Dennis J. Slamon, MD, PhD, standing on the starting line.
Slamon, now director of Clinical/Translational Research at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA), conducted the laboratory work and testing that resulted in trastuzumab (Herceptin), the first molecularly targeted therapy for breast cancer. The monoclonal antibody made by Genentech helps counteract a mutation of the HER2 gene, which is found in about 25% of patients with breast cancer. It reduces recurrence rates by half in specific types of early HER2-positive breast cancer and by one-third in metastatic HER2-positive breast cancer, and increases survival rates by about 35% and 30% in early and metastatic disease, respectively, according to the researcher.
The intravenously administered medication was approved by the FDA in 1998, and within 10 years, it had been used to treat 420,000 women worldwide. Its approval also marks the moment that the area of targeted therapies for cancer really began to take off.
“That’s the area where things are moving the fastest—finding molecular heterogeneity and taking advantage of that to develop novel therapeutic approaches for subtypes, rather than one-size-fits-all approaches,” said Slamon. “That’s where a lot of effort is going on, not just by us, but in a number of labs around the world. Trastuzumab was one of the things that really broke that wide open.”
It’s an accomplishment that made Slamon the subject of both a Lifetime television movie, Living Proof, and a book by Robert Bazell, HER-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer. His is a particularly intriguing story because the scientist had to fight for 12 years to get trastuzumab from development through approval, keeping the project alive despite a nearly crippling early lack of funding.
“We followed the data, and if it’s there and it says your approach is right, it doesn’t matter what anyone else’s preconceived notion is,” Slamon said. “We never gave up when people said we were wasting our time.”
Those achievements have been heralded worldwide, and they are certainly appreciated by OncLive. For bringing the world trastuzumab, helping to launch an important new path for cancer research, and developing additional promising anti-breast cancer drugs during a career that has spanned about 40 years, Slamon has been selected as one of OncLive’s Giants in Cancer Care for 2014, in the Breast Cancer category.
“I was honored, as I think were all the honorees, and I felt very good about being named among those peers,” Slamon said upon learning he would receive the award.Striving For Further Discoveries
These days, Slamon is continuing his fight against cancer through his roles at UCLA. Serving as chief of its Division of Hematology-Oncology and also as a professor of Medicine, the doctor devotes about 30% of his hours to administrative duties, including raising money for research; another 20% to seeing cancer patients; and a small percentage to teaching and giving lectures.
He spends the remainder of his time—nearly half—reviewing data and considering where it might lead.
“The highlight of my day is to meet with mid- and junior-level investigators and see this new stuff,” he said. “With colleagues capable of pushing the agenda in a positive way, we can think about exciting ideas.”
One of the most promising recent developments to come out of Slamon’s lab has been palbociclib, an oral inhibitor of CDK 4/6 that was developed for the treatment of hematopoietic malignancies but was only mildly active in that cancer type. In February, the FDA granted accelerated approval to palbociclib, which Pfizer developed under the trade name Ibrance, in combination with letrozole as a first-line treatment for HER2-negative advanced or metastatic breast cancer in postmenopausal women.
Another project of Slamon’s lab has involved BMN 673, a PARP inhibitor being developed by BioMarin that targets BRCA1/2 mutations in patients with locally advanced or metastatic breast cancer, but that also may have promise for the treatment of triple-negative breast cancer, some breast cancers, and other malignancies, Slamon said. The drug is being tested in a phase III clinical trial.
Not surprisingly, Slamon and his colleagues are also continuing to work with trastuzumab.