UCSF Chancellor Susan Desmond-Hellmann delivers the keynote address at the UCSF Helen Diller Family Comprehensive Cancer Center’s Breast Oncology Program on Jan. 28.
Golden Age of Drug DevelopmentDuring her talk, Desmond-Hellmann referred to the years from 1997 to 2001 as the golden years. It was then that the drugs Rituxan, Herceptin and Gleevec became widely available for treatment, with each having a great impact on patient survival and in changing the ways that researchers and physicians think about cancer. UCSF can play an important role in initiating a new golden age of drug development, Desmond-Hellmann says. Rituxan, the first monoclonal antibody approved for treatment of a human cancer -- non-Hodgkins lymphoma -- was special because of its rapid approval and launch, Desmond-Hellmann says. “The pivotal trial for Rituxan had 166 patients. … It was uncontrolled, because the standard therapy for non-Hodgkin’s lymphoma at the time was to watch-and-wait, to avoid the complications of not-effective-enough chemotherapy. “The cure rate significantly increased,” Desmond-Hellmann says. “And one of the most interesting aspects that’s still under study, is this possibility of turning cancer into a chronic disease,” in the same way that HIV infection is regarded as a chronic but not necessarily rapidly fatal condition. Herceptin is a type of personalized medicine aimed at a protein called Her2 that is abnormal in a subset of breast cancers. Its presence is associated with a worse prognosis. “The rapid FDA approval was due to a large unmet need and to patient advocate demands,” Desmond-Hellmann says. “Before [Herceptin] there was no treatment option specific to Her2-positive breast cancer, and it was a rapid death sentence for most women. … After, there was about a 20 percent difference in disease-free survival at five years, and the new therapy reduced the chance of cancer returning by 52 percent. “Gleevec was the perfect storm of discovery, advocacy and commitment,” Desmond-Hellmann says, “with a fast FDA approval and a phenomenal success rate in treating chronic myelogenous leukemia (CML). Before Gleevec only 30 percent of patients with CML survived five years after diagnosis and treatments have serious side effects.” Now there is a complete hematological response in more than 98 percent of patients and a 90 percent five-year survival rate, she says. “These are the kinds of outcomes we should strive for in hematology-oncology,” Desmond-Hellmann says. So why are we no longer witness to golden years for the development of cancer-fighting drugs?
UCSF Chancellor Susan Desmond-Hellmann, center, talks with molecular biologist Laura van 't Veer and Frank McCormick, director of the UCSF Helen Diller Family Comprehensive Cancer Center.
Promising TreatmentsDesmond-Hellmann mentioned four examples of treatments as holding as much promise as the drugs of the golden years. They are targeted at different molecules and biochemical pathways. Certain types of cancer depend on the biochemical activities of these targeted molecules for their survival. One category includes drugs that inhibit the action of a protein called BRAF. BRAF drives as many as 60 percent of malignant melanomas, and eight percent of solid tumors, Desmond-Hellmann says. Another group of promising drugs in development targets the “hedgehog” biochemical pathway in basal cell carcinoma, a type of skin cancer, and in some forms of medulloblastoma, a deadly brain cancer. About five percent of patients with lung cancers may greatly benefit from drugs that target a protein called ALK. The last group of promising drugs mentioned by Desmond-Hellmann inhibits the action of the protein called PARP. These show promise in treating the most difficult-to-treat “triple negative” breast cancers, which lack three more common markers found in many breast cancers. To help make drug development faster, cheaper and more predictable, Desmond-Hellmann says, “We need to understand earlier and with greater confidence what the best ideas are.” “I think we should be extremely dogged -- even if it’s for a narrow group of patients -- to uncover those cancers driven primarily by a single [biochemical] pathway.” Disrupting such an important lifeline for these cancers could have a great impact on patient survival. To explore the potential of combination therapies, Desmond-Hellmann says, “We need to understand how to test more than one product at a time and to do it efficiently, in a way that gives us clear signals.” Desmond-Hellmann cited the need for better early markers of success or failure in clinical trials. “I think survival is the best outcome measure, but if survival is extended, I am not willing to wait beyond our lifetimes to know the answer, and more importantly patients should not have to wait.” What is learned in clinical trials or even after drug approval can be used to guide future research, Desmond-Hellmann says. “There is no reason in today’s world, with electronic medical records and information technology that we shouldn’t know what happens with every patient. We need both outcomes and molecular correlates on every cancer patient. … There is so much information on safety, efficacy, potential good and potential harm, and we need to have that.” Desmond-Hellmann notes that affordability and patient access to the best treatments are important issues. “We need to make sure that the right product reaches the right patient at the right time and that the patient has access to it.” For each cancer patient, the goal is to be able to say, “Here’s the kind of cancer you have, and in fact, we have something for that.” UCSF has an unprecedented opportunity and great talent to contribute to accomplishing this goal, Desmond-Hellmann says.
Advancing Ideas More QuicklyIn an interview after her keynote address, Desmond-Hellmann elaborated on points she made during her presentation and discussed ways in which academic researchers can work with industry and patient-advocate groups to advance promising treatment ideas more quickly.
Medical oncologist Hope Rugo talks with UCSF Chancellor Susan Desmond-Hellmann while Thea Tlsty, professor of pathology, looks on.
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