Helen Diller Family Comprehensive Cancer Center Showcases Research Progress

The UCSF Helen Diller Family Comprehensive Cancer Center hosted an afternoon event on the Mission Bay campus on May 12 to showcase recent progress and current research directions in the fight against cancer. Plenary session speakers included UCSF Chancellor Susan Desmond-Hellmann, MD, MPH, Frank McCormick, PhD, director of the Cancer Center, and James Wells, PhD, who heads the Small Molecule Discovery Center. All three came to UCSF after driving drug development projects in industry. Breakout sessions followed. Each was focused on specific types of cancer. The showcase event concluded with a reception and an update on the construction of UCSF Medical Center at Mission Bay from Mark Laret, chief executive officer of UCSF Medical Center. All three plenary speakers noted recent progress in understanding and treating cancer. But they also spoke of ongoing challenges to research and patient care, including the need to know if treatment is likely to be effective for a particular patient, and the need to know early on whether the treatment given to a patient is working.

Developing New Strategies

McCormick emphasized the central role UCSF researchers play in cancer research. He noted the strong UCSF participation last month at the annual meeting of the American Association of Cancer Research (AACR) -- the nation’s most prominent professional organization for researchers who aim to better understand cancers -- and the potential vulnerabilities of tumors that might be exploited in developing new treatment strategies. McCormick touched on clinical strategies that are being explored at UCSF, including combination treatment to overcome drug resistance; emerging therapies aimed at stimulating the immune system to attack tumors; and the use of small interfering RNA (siRNA) molecules as drugs to stop the activation of genes that tumors rely on. Wells noted that most drugs used to fight cancers inhibit proteins needed by tumors. However, Wells’ latest strategy is to try instead to activate a protein. The target for activation is called caspase 3. Caspase 3 triggers a biochemical chain reaction leading to cellular suicide. Normal cells usually activate this suicide program for the greater good when they become abnormal and cannot repair themselves. Tumor cells shut down this suicide program. Wells aims to turn it back on, and already he has had success treating cells on the lab bench. Desmond-Hellmann spoke about the need to develop more powerful and faster ways to evaluate drugs in clinical trials. She also talked about success stories – powerful new treatments for cancer developed using knowledge gained from basic research. The drug Gleevec was among the success stories Desmond-Hellmann mentioned. Academic researchers and patient advocates played a driving role in the development of the drug, which has greatly improved the survival prospects for patients diagnosed with the blood cancer called chronic myelogenous leukemia (CML). Prior to Gleevec, most patients with this disease died. Today, most survive, she said. But Gleevec also provides researchers and physicians with a refresher on drug resistance, which McCormick earlier described as a continual challenge to the development of successful long-term cancer therapies. Within two years of treatment, Gleevec no longer holds cancer at bay in many patients. Fortunately, research at UCSF and elsewhere is leading to drugs that may help oncologists keep one step ahead of CML and other cancers.

Making Progress on Blood Disorders

Physician-scientists who lead UCSF efforts to better understand cancers that arise in different types of cells found in blood -- leukemias, lymphomas and myelomas – described ongoing research during one of the breakout sessions. Kevin Shannon, MD, leader of the Hematologic Malignancies Program for the UCSF Helen Diller Family Comprehensive Cancer Center, introduced the session by explaining how blood cancers differ from solid tumors. Blood tumors derive from stem cells, Shannon explained. These particular stem cells give rise to all cells of the blood system. The myeloid cells include platelets, red blood cells and neutrophils. Lymphoid cells include B and T lymphocytes. The stem cells also allow bone marrow recipients to regenerate the blood system. Different blood cancers may arise from stem cells that are at different stages of maturation, Shannon said. Specialized blood cells differ from many other tissues in that they normally live only a short time and continually must be replaced by new cells. Blood cancers tend to be widespread in the body by the time a patient is diagnosed. Therefore, surgery and radiation treatments are not normally treatment options. Instead, patients are given drugs that attack blood cancer cells throughout the body. While there is far to go to improve treatments for blood cancer patients, survival has greatly increased in recent decades, panelists noted. Ten years ago patients with myelomas survived about two years on average. Now average survival is about six years, according to the panelists. When Shannon began treating children with leukemia years ago, these young patients predictably relapsed despite treatment. Now the survival rate is about 85 percent, Shannon said. With steady advances in scientists’ understanding of these cancers and the new treatment strategies that follow from this new knowledge, Shannon said, “At the end of the day, these remission rates … turn into real cures.” Panelist Neil Shah, PhD, MD, co-leader of the Hematologic Malignancies Program for the Cancer Center, discovered a key mechanism that explains how CML can develop resistance to Gleevec. Shah is expanding his studies to explore the potential value of other small-molecule drugs in treating CML and other diseases, including acute myeloid leukemia and myeloproliferative disorders. Jeffrey Wolf, MD, director of Clinical Research and of the Myeloma Program for the Division of Hematology/Oncology within the Department of Medicine at UCSF, described how research is organized within UCSF's new Multiple Myeloma Translational Initiative. The initiative was launched last year, driven by a $2 million gift from Stephen and Nancy Grand, longtime supporters of UCSF. The program has been bolstered by funding from the Howard Hughes Medical Institute. The initiative brings several world-class scientists from UCSF into the myeloma research arena, where they are exploring novel drug strategies in animals with blood cancers. Wolf and Thomas Martin, MD, associate director of the UCSF Myeloma Program and director of the Matched Unrelated Donor Transplantation Programs for adults at UCSF Medical Center, also discussed clinical research to evaluate experiment treatments for myeloma and leukemia. Mignon Loh, MD, a pediatric cancer specialist with the UCSF Department of Pediatrics, briefly described her studies of pediatric blood cancers. Loh identified a mutated gene that plays a crucial role in about one-third of juvenile myelomonocytic leukemia cases, and a second mutation responsible for another 15 percent of these cancers. After studying the biochemistry of how these mutations drive cancer growth in mouse models and after testing a molecule that could potentially be used to treat the disease in these mice, Loh is planning to launch a clinical trial to treat patients with the new drug candidate later this summer. Certain blood cancers, such as non-Hodgkin’s lymphoma, are becoming more common in the United States. In response to audience questions, panelists noted that while much has been learned about specific genetic mutations that are associated with certain blood cancers -- including some mutations that arise in the fetus -- little is known about environmental contributors to these cancers. Photos by Noah Berger

Related Links:

• UCSF Helen Diller Family Comprehensive Cancer Center
• UCSF Medical Center -- clinical care for leukemia
• UCSF Medical Center -- clinical care for lymphoma, Hodgkin's, non-Hodgkin's
• UCSF Medical Center -- bone marrow transplant procedures