UCSF Helen Diller Family Comprehensive Cancer Center

Transcription

1 Care. heal. UCSF Helen Diller Family Comprehensive Cancer Center 2015 Cancer Showcase Report

2 A State of the Science on Cancer A cancer is as unique as the individual life it threatens. The disease is driven by each cancer s unique genomic fingerprint and is experienced in ways that are profoundly personal. At UCSF s Helen Diller Family Comprehensive Cancer Center, we are engaged as never before at every level of the disease from the micro-details of individual genes to the big picture of the patient s experience. At the 2015 Cancer Showcase, 30 of our basic, clinical, and population scientists shared their progress in a wide range of areas, from big data to quality of life. We ve communicated these advances in the pages that follow. Each session was remarkable, and taken together, they describe the state of cancer science and it is compelling indeed. Whether in our search for new therapies or our efforts to enhance care, people will continue to be at the heart of our mission. We are going to look at the whole experience of the UCSF cancer patient from his or her first visit, hopefully through cure and survivorship; and if not, then through ending their journey with dignity. As one example of many steps being taken toward enhancing the patient experience, we are introducing palliative care earlier and more comprehensively in cancer care. To hasten the time it takes to get discoveries out of the lab and to our patients, we are developing integrated teams focused on specific diseases. These teams will combine our deep disciplinary strengths in fields such as cellular and molecular biology, population science, and computational biology to give us an unprecedented breadth of perspective. From there we will create rapid, systematic steps from the lab to the bedside and back again to hone and translate our discoveries into safe and effective treatments. Central to our vision is the Precision Cancer Medicine Building. This 170,000-square-foot facility, to be constructed at Mission Bay, will allow us to be at the forefront of what has now become a national priority with President Barack Obama s announcement of the Precision Medicine Initiative. We also are developing an innovative Center for BRCA Research with an integrated patient clinic. It will be the culmination of my long-sought goal of creating a comprehensive research and treatment approach for BRCAmutation carriers. The center will be a microcosm of our overarching strategy to bring basic research through translation and into the clinic as quickly and as accessibly as possible. Please page ahead for a sense of where we are and where we are headed. As you read, know that we owe our place at the very top of the field of cancer research and care to those whose generosity helped get us here, and who we regard as true partners in the future. Many thanks, Alan Ashworth, PhD, FRS President, Helen Diller Family Comprehensive Cancer Center

3 Cancer Genomics Boris Bastian, MD, PhD Kristen McCaleb, PhD Cancer genome sequencing reveals which gene mutations are associated with which cancers such as breast cancer s link to the BRCA gene mutation or leukemia s link to the BCR-ABL mutation and provides insight into related mutations that may cause cancers in different parts of the body. Through UCSF s Cancer Genetics and Prevention Program, the largest such center in Northern California, genomic testing can provide lifesaving preventive options for children in families with a history of cancer. Likewise, they can search the database for patients with similar genetic profiles to their own patients to determine the best care options and outcomes. In this way, the database, or knowledge network, becomes a continually evolving, virtual clinical trial of cancer care. UCSF, already a leader in the field, has roles on statewide and national precision medicine initiatives that will help it accelerate the study of cancer genomics and translate those findings seamlessly from the research community into patient care. Developing New Cancer Drugs UCSF launched the Genomic Medicine Initiative two years ago with the goal of building a powerful Steven DuBois, MD infrastructure and electronic medical record system to Frank McCormick, PhD, FRS, DSc serve as the linchpin of its precision medicine effort. In Pamela Munster, MD partnership with software company Syapse, UCSF is Jeffrey Wolf, MD creating a sophisticated database for clinicians to record patient data, genomic testing and analysis, treatment Basic and clinician scientists at UCSF have been at the plans, and outcomes. forefront of drug discovery for decades and have great insight into the changing nature of the endeavor over Incorporated into the software is the UCSF 500, a time. The sequencing of the genome confirmed that panel of 500 gene mutations implicated in cancer and genes were driving the mutations that caused cancer. catalogued by UCSF oncologists. Physicians continually Isolating the particular gene that drove specific cancers upload their patients data to share their treatment led to lifesaving drug discoveries. Yet as the field has strategies and outcomes. progressed, researchers have found that few cancers have just one driver. Tumors can grow over two to three decades, acquiring as many as 40 different mutations. Trying to figure out which mutations drive the disease is far more complicated than once thought. Consequently, the next wave of cancer treatment is combination therapy agents that boost a patient s Frank McCormick, PhD, FRS, DSc Boris Bastian, MD, PhD

4 immune response coupled with drugs that bombard the cancer itself. In UCSF s Developmental Therapeutics program, clinician-scientists go back and forth between their clinics and labs to develop drugs for their patients who have run out of options. They sequence the DNA of the patients for inherited cancer-causing mutations, and then Enhancing Quality of Life for Cancer Patients, Survivors, and Their Families Susan Chang, MD Lee-may Chen, MD Michael Rabow, MD Treating cancer once meant choosing between quality or quantity of life. But this is no longer true, according to researchers at the UCSF Helen Diller Family Comprehensive Cancer Center. UCSF Chancellor Sam Hawgood s opening remarks sequence their tumors for precise targets. If a patient s tumor becomes resistant to a therapy, the clinicianscientists head back to the lab to find the next target, while looking closely at the tumor environment for new immunotherapy options. A great number of drugs are under development at UCSF, adding to a long list of our successes, including sipuleucel-t, the first FDA-approved cancer vaccine, and ipilimumab, the first FDA-approved immune checkpoint inhibitor. UCSF scientists also are hard at work on a new therapy for Ewing s sarcoma, a rare pediatric bone cancer. While the current treatment is effective, its side effects are debilitating as the cured former patients age. Efforts are underway to change dosage and delivery methods, in addition to looking for substitute drugs to solve the issue. Scientists at UCSF also are adding drug candidates with great potential for success for myeloma, an adult bone cancer. Cancer treatment at UCSF now routinely incorporates palliative care, a range of services designed to address mental, emotional, and spiritual symptoms and maintain quality of life while simultaneously administering the best oncologic treatments available. The cancer center offers palliative care through several multidisciplinary teams and services, including symptom management, psycho-oncology, social work, spiritual care, and caregiver support. These services provide help with pain, fatigue, depression, insomnia, anxiety, and spiritual issues, all integrated into regular oncologic care. Family members and caregivers also can get training and support. Research, while still in its early stages, demonstrates that patients who receive palliative care at the time of diagnosis feel better, have less pain, and are likely to live longer. As one of the nation s pioneers in palliative care, UCSF is striving to make this level of care available for all cancer patients, whether their disease is life-threatening or not, to help them live as long and as well as possible. UCSF researchers give credit to patients and their families for their invaluable feedback along the way. These dynamic

5 relationships between UCSF practitioners and patient families have led to higher touch, more comprehensive, and lasting clinical care programs. The New Generation of Cancer Researchers: What s on the Horizon for Us? Chloe Atreya, MD, PhD Trever Bivona, MD, PhD Adam De Smith, PhD Kyle Walsh, PhD UCSF s young cancer researchers see promising trends on the horizon. First is an unprecedented level of collaboration among universities. Increasingly, large grants are awarded to multiple institutions, featuring as many as 40 authors across various universities and disciplines. They have also seen a decrease in drug development times over the last five or six years with the emergence of sophisticated molecular techniques to identify specific treatments for specific patients. In fact, several breakthrough therapies for lung cancer that spent only two or three years in the development process may be approved in late Kyle Walsh, PhD They note an increase in the use of drug cocktails in cancer, where as many as three therapies compensate for each other s shortcomings. The researchers spoke of a therapy cocktail that shrunk tumors in only about 12 percent of patients, but for one, it has kept cancer at bay for three years. Now researchers seek to answer why, in hopes that the solution will lead to a more broadbased cure. Another trend cited was the national shortfall in funding for early-career researchers like themselves. Consequently, young investigators all over the country take significant time away from their research to pursue grants. Funding from endowments proves most valuable in allowing them to return to their work. Often, donor support equates to seed grants, funding research that enables younger researchers to collect enough primary data to then apply for federal and other grants. The Perils of Over- Diagnosing Cancer Matthew Cooperberg, MD, MPH Laura Esserman, MD, MBA In the 1980s, national recommendations emphasized rigorous screening and early detection as the keys to reducing the rate of late-stage disease and decreasing cancer mortality. While aggressive screening has increased early-stage Laura Esserman, MD, MBA detection, it has failed to produce a significant drop in later-stage disease and morbidity rates.

6 With the release of reports showing screening efforts cost the US $4 billion annually in unnecessary treatment costs, the National Cancer Institute convened an advisory panel of the most innovative oncologists to evaluate overdiagnosis. They sought out Laura Esserman, MD, MBA, to chair the panel. According to Esserman, considering all cancers as lethal leads to overtreatment. Cancer is not one disease with a standardized treatment. The more we know about a cancer, the more we can avoid a one-size-fits-all approach and adapt treatment to a person s specific case by developing targeted therapies. Overtreatment doesn t have to be the price of screening the general population. Matthew Cooperberg, MD, MPH, has identified patterns and outcomes in the diagnosis and treatment of urological conditions that often lead to overtreatment. He was recently recognized by the American Urological Association for this groundbreaking research. Our clinician-scientists are using biology and genetics to drive treatment choices and reduce the possibility of overtreating a cancer that, though detectable, may never kill. At UCSF, more personalized care and treatment options allow our practitioners to think about the entire patient ecosystem, develop treatments specific to their biology and genetics, and provide more rational and directed care. Big Data and Cancer Michael Blum, MD Atul Butte, MD, PhD Eric Collisson, MD Big data has radically changed the way medicine is practiced at UCSF. Eric Collisson, MD, conveyed its power with the story of a patient who was referred to him with all the classic signs of pancreatic cancer. Yet in sequencing her genome, Collisson found that the patient carried the BRCA2 mutation and that her cancer was actually ovarian. A database search of her genetic signature showed evidence that platinum therapy had halted the cancer in others. The genetic re-diagnosis saved her life and perhaps the lives of her three children, as the mutation is inheritable, and the cancer now is treatable with a PARP inhibitor, a drug developed for BRCA-related cancer by UCSF Helen Diller Family Comprehensive Cancer Center President Alan Ashworth. Atul Butte, MD, PhD Called precision medicine (see first session on Cancer Genomics), the new field incorporates not only genomic data but also environmental, lifestyle, and behavioral health information, including some delivered in real time from wearable devices. As director of UCSF s Center for Digital Health Innovation, Michael Blum, MD, helps incubate UCSF discoveries in the digital space, validates existing technology, and partners with industry to create new ones. UCSF, as one of the UC system s five medical centers, will host the second largest health database in the world, with 13.6 million electronic health records. Atul Butte, MD, PhD, director of UCSF s Institute for Computational Health Sciences, will spearhead UCSF s efforts to best leverage this invaluable resource. Virtual clinical trials, enrolling not just across all five centers but also across the world, will be run using highly selective patient groups, promising more precise results at a fraction of the cost and time. The impact on rare cancers will be profound because clinicians will finally be able to build statistically significant

7 numbers of patients for trial with people participating from remote locations all over the world. Cancer Immunotherapy Lawrence Fong, MD Lewis Lanier, PhD Immunotherapy has transformed the treatment approach to cancer. Even the language traditionally used to describe cancer treatment is no longer appropriate. What used to be referred to as the fight against cancer Lawrence Fong, MD is now more likely to be presented as a strategic bolstering of the immune system. UCSF is leading the way because a new generation of drugs developed here has successfully reduced tumor size and eliminated clinical evidence of some cancers formerly considered incurable. Cancer confounds the immune system into complacency and leaves the body susceptible to malignant disease. New immunotherapy treatments awaken a patient s immune system, eliminate abnormal cell growth, and build up the immune system to unleash its power. Whether on its own or in concert with other treatments, immunotherapy involves genetically engineering T cells the soldiers of the immune system to give them the power to attack infected cells and demobilize invading pathogens that previously eluded them. Normally considered untreatable, people with late-stage melanoma rarely live more than a few months. But in a 12-site clinical trial, 80 percent of participants who responded to immunotherapy were still going strong two years later, and 15 to 20 percent who had terminal melanoma are considered cured. These drugs were brought from successful mouse models into FDAapproved treatments in less than a decade. It is not surprising that word of the success spread quickly and led to an explosion of interest. With such promise, UCSF scientists are studying success rates and patient response in hopes of understanding when the immune system can be unleashed to fully respond to the threat of cancer at a molecular level. Now the possibility of a cancer vaccine is no longer a distant dream but a predictable reality. Cancer Prevention Strategies June Chan, DSc Stacey Kenfield, DSc Greta Macaire, MA, RD, CSO Erin Van Blarigan, ScD There s no guarantee against cancer risk. People who eat a healthy diet, exercise regularly, and never smoke still sometimes get cancer. However, scientific evidence including some gathered at UCSF shows that a healthy diet and lifestyle June Chan, DSc can reduce your risk of cancer by 15 percent. Our clinician-scientists shared prevention strategies and the evidence to back them up: Avoid smoking or chewing tobacco. Nearly one-third of cancer deaths in the US result from tobacco use.

8 Exercise for 30 minutes or more, at least five days a week. Exercise in any form helps avoid cancer. If you can t do 30 minutes at a time, you can get the same benefit from three 10-minute bouts during the course of the day. Sitting is the new smoking. Limit sedentary activities such as watching TV and working at a computer. Being sedentary increases the likelihood of cancer, heart disease, obesity, diabetes, and other diseases. Stand up and move around for a few minutes every hour. Plan trips to the bathroom, copier, etc., around that schedule to limit the sedentary period. Limit damaging foods, including red meat, alcohol, and foods high in sodium. A Disproportionate Burden of Cancer Rena Pasick, DrPH Eliseo Perez-Stable, MD Gideon St.Helen, PhD Janice Tsoh, PhD African-American men with prostate cancer have twice the mortality of their white counterparts. Latinos are more likely than any other US group to be uninsured. Asian- Americans account for half of all US liver cancers. These are just a few examples of the disproportionate burden of cancer suffered by vulnerable US populations. Avoid sugar-sweetened beverages, including soda and fruit juices, which promote weight gain and obesity. Obtain nutrients from food, not supplements. Eating a plant-based diet fruits, vegetables, whole grains, and legumes increases your intake of protective substances like dietary fiber, vitamins and minerals, and phytochemicals that deter cancer development, and also makes it easier to maintain a lower calorie intake. Research also indicates that if you are diagnosed with cancer, a low-fat diet and vigorous physical activity for at least three hours a week reduces your risk of dying from the disease or having it recur after treatment. Rena Pasick, DrPH UCSF s Helen Diller Family Comprehensive Cancer Center is a national leader in cancer disparity research on the causes of these gaps, which include low income, poor education, limited English proficiency, and lack of medical insurance. Also contributing are a lack of diversity in clinical trials and limited access to highquality care. Cancer and public health experts at UCSF are developing interventions to reduce such disparities through outreach, education, and training. Most effective, they say, are collaborations with trusted community sources, such as churches and lay health ministries, as well as counseling and awareness campaigns to promote cancer screenings and genetic testing among at-risk populations. Underway through the National Cancer Institute is the Minority Training Program in Cancer Disparities, a 10-year effort to strengthen and increase diversity in the field of cancer disparity research. Also needed are ongoing efforts to increase understanding of the correlation between low socioeconomic status and poor health The Regents of the University of California