There was a time when our only weapons against cancer were blunt ones—chemotherapy and radiation that kill diseased cells but do considerable damage to healthy tissue along the way.
Fortunately, a dramatic shift has been occurring. Bold ideas about more-targeted, less-toxic therapies have begun to enter the mainstream. And Dr. David Maloney has played a pivotal role in getting them there.
Maloney's work focuses on developing and improving cancer therapies that take advantage of antibodies—proteins formed in our blood to fight invaders. This approach falls into a class of treatments known as immunotherapy, which harnesses the power of the body's immune system to fight disease.
Maloney and his colleagues have also made important improvements to stem cell transplantation treatments for a variety of blood cancers. For multiple myeloma patients, they pioneered the use of a multistep procedure that involves an infusion first of the patient's own stem cells and then of donor cells. They also introduced the use of reduced intensity, or non-myeloablative, transplants for patients with low grade lymphoma, aggressive lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia, demonstrating high response rates and long-term remission.
As a doctoral and medical student in the early 1980s, Maloney was part of a Stanford University team that made a landmark discovery. They found that it is possible to create and deliver special antibodies that target a patient's cancer cells—in this case, non-Hodgkin's lymphoma—but largely spare normal cells.
"At that time there was much skepticism that antibodies would amount to anything," Maloney recalled. "It has ended up now being a mainstay of cancer therapy."
These early research successes led to the development of a widely used drug called rituximab, which works by targeting a protein unique to many lymphoma tumors. The major benefits of this approach, Maloney said, are that the antibodies are relatively simple to produce in great enough quantities to serve many patients and that they generally produce few toxic side effects.
After leading the original clinical trials of rituximab with promising results, Maloney brought his expertise to the Hutchinson Center's faculty in 1994. Three years later, the Food and Drug Administration approved the drug, making it the first antibody-based cancer treatment on the market. Under the brand name Rituxan, the drug has since been used to treat more than 1 million patients with non-Hodgkin's and follicular lymphomas.
"It's the biggest breakthrough in lymphoma therapy in the past 25 years," Maloney said. "It has been paradigm changing."
The success of rituximab has also helped to propel the creation of other antibody-based therapies, including ones to treat leukemias, colon and breast cancer. Some drugs also combine the antibodies with dosages of chemotherapy or radiation in an effort to deliver a more direct hit of toxins to the malignant cells while sparing surrounding tissue.
Meanwhile, there's still a push to make a more effective rituximab, Maloney said. Although the therapy has been shown to prolong survival, not all patients respond well, and they can develop resistance over time. Maloney's ongoing research explores how treatments for lymphoma, multiple myeloma and chronic lymphocytic leukemia could be more effective by combining antibody treatments with different chemotherapy regimens and stem cell transplantation. He and his Hutchinson Center colleagues are also working to identify additional proteins on cancer cells that antibodies can more readily target.
In addition to investigating exciting new treatments, Maloney sees lymphoma patients regularly through the Seattle Cancer Care Alliance, the Center's treatment arm.
"Seeing patients always gives you perspective on the disease you're treating," he said. "I view oncology as more than just a snapshot, but managing challenges with cancer over a long period of time."