pancreas cancerStopping Cancer in Its Tracks

FROM THE DIRECTOR

A Whole Greater Than the Sum of Its Parts

UCSF enjoys an outstanding reputation for how we care for patients with all types

of pancreas disease and for the research we conduct.

Nevertheless, treatment approaches for conditions of the pancreas remain limited. Pancreas cancer continues to be the fourth leading cause of cancer deaths, and the overall survival rate is only 6 percent. This is a real call to action!

In particular, we must foster enhanced integration and collaboration among researchers and clinicians across multiple disciplines. That’s precisely the thinking behind the UCSF Pancreas Center – a vision for a linked set of multidisciplinary, patient-centered clinics that will move research discoveries as swiftly and safely as possible into better and faster diagnoses and treatments.

Consider the strengths on which we can build.

From the research end, we have a growing and world-class team of dedicated scientists and clinicians who conduct innovative lab studies and clinical trials that test better treatments for all pancreatic conditions. Our newly launched CAPTuRe program provides a framework to optimize our cancer research by

By growing up on a farm, John P. Morris IV, PhD, learned, “We are often at the mercy of unpredictable

nature.” That lesson deepened at Harvard

University where, as an undergraduate, Morris worked in a lab studying cancer in zebrafish and realized that the disease is another example of being at the mercy of nature’s unpredictability. If, however, he could understand cancer formation enough to make it predictable, he thought this could hold the key to beating the disease.

That theory found a home when Morris arrived at UCSF and began working with renowned developmental biologist Matthias Hebrok, PhD, Hurlburt-Johnson Distinguished Professor in Diabetes Research. “Matthias believes cancer is developmental biology gone wrong,” says Morris. Through research programs funded by the National Institutes of Health and Pancreatic Cancer Action Network, Morris’ work in the Hebrok lab – both as a student and, now, as a post-doctoral researcher – strives to render that developmental process predictable and, ultimately, treatable.

Specifically, Morris studies the formation of pancreatic ductal adenocarcinoma (PDA), the most common form of pancreas cancer and fourth leading cause of cancer-related deaths. In most cases, by the time PDA is diagnosed it is too late for surgery, the only effective therapy at this point.

Morris hopes his work can change that dynamic. “From mouse models, we’ve learned that for pre-cancerous lesions and cancers to form, a complex set of signaling pathways and transcriptional events need to be precisely regulated in time- and level-dependent ways,” he says. His

studies attempt to rigorously map that process, in the hope that targeted therapies can effectively disrupt or even reverse it.

Morris’ work has zeroed in on KRAS, a protein encoded by the KRAS gene that is associated with many different forms of cancer, and is mutated in 90 to 95 percent of all PDAs.

The studies track complex interactions in the pancreas where mutant KRAS appears to “instruct” cells to move toward a pre-cancerous state. For example, one research path focuses on the aftermath of acute pancreatitis, when damaged cells in a healthy pancreas begin to regenerate, a common process.

“When KRAS mutation is present, the regenerative environment changes,” says Morris. Cells lose the ability to regain normal differentiation, creating a permissive environment for pre- cancerous lesions to form (pictured at top of page).

“If we can pinpoint what mutant KRAS needs to start the process, we might be able to effectively disrupt it, or create therapies that can kill cells with mutant KRAS as they progress towards PDA,” he says.

Even if therapies cannot be developed quickly, Morris hopes that within a decade, the work will at least identify an effective marker for who is at risk for the disease. This could lead to the earlier detection needed for effective surgery.

Then, Morris hopes, pancreas cancer patients won’t be quite so vulnerable to the whims of nature.

Continued on next page

John Morris

Margaret Tempero

newsSPRING 2012

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making the most of every precious tissue sample, standardizing protocols, and efficiently dissemi-nating key information to various research teams.

Clinically, our specialists are world leaders in the diagnosis and treatment of all types of pancreas tumors – benign and malignant. Cancer specialists in medical oncology, surgery, radiation, physiology, nutrition and nursing ensure that each individual receives the best combination of therapies for his or her particular condition, body, mind and life outside the hospital.

The UCSF Pancreas Center will draw this work together under one virtual roof, creating a holistic effort that is far greater than the sum of its parts. The center will receive an additional boost when we eventually create a physical home for this work at Mission Bay – a hothouse of scientific innovation.

We are grateful to those who have combined to pledge $10 million in endowment to date toward realizing this vision. These inspiring commitments will provide support for leadership, expert nursing care around the clock for pancreas patients, and new investigators.

We know these are trying economic times and scientific funding is scarce. With time and additional support, we hope to recruit the best scientific minds in the world to collaborate together at UCSF. With better strategies for early detection and more effective treatments, we will conquer this disease.

With your help, we can make that happen.

Sincerely,

Margaret Tempero, MDLeader, Pancreas Cancer ProgramDoris and Donald Fisher Distinguished Professor in Clinical Cancer Research

Marilyn Amsden In 2007 I was diagnosed with incurable Stage IV pancreatic cancer – specifically rare slow growing neuroendocrine tumors. This news was devastating to me and my family. At the time I was not a candidate for surgery, chemotherapy or radiation. The dedicated staff at UCSF provided me alternatives to more traditional treatments. In particular, doctors Alan Venook and Emily Bergsland, and dietician Greta Macaire, recommended that I take monthly shots of Octreotide Lar, change my diet in order to strengthen my immune system, and increase my daily exercise. Last year, because of tumor growth, I was enrolled at UCSF in a clinical trial using everolimus. Through the care I have received at UCSF and the prayers of my family and friends, we have successfully reduced my symptoms and stabilized some of the tumor growth.

WHY I GIVE TO UCSF: Research funding for rare forms of cancer is critical to our understanding of this devastating disease. In 2009 and 2011 my son Jeff rode in the Leadville 100 and Leadville 50, mountain bike races at extreme elevations in Colorado, to help raise money for neuroendocrine tumor research at UCSF. My other son Dan designed the fundraising website (www.amsdenchiro.com/marilynamsden.html), which we use to reach out to family and friends for support. To date we have raised $25,000, which has gone directly to Dr. Bergsland’s research and clinical trials on neuroendocrine tumors at UCSF. Everyone I have come in contact with at UCSF I consider a friend. They are brilliant people who are also very caring, concerned and thoughtful.

Stuart Rickerson I’m from San Diego. When I was in the hospital there recovering after my surgery, my wife, God bless her, put together a “roadshow” to see some of the top oncologists in this field in the country for when I got out. UCSF was my fifth stop. When we got in the elevator at Mt. Zion after meeting with Dr. Margaret Tempero, and I pushed the button for 1 coming down from 4, I said to Nancy, “We don’t have to go to any of those other centers. This is the place.” And that’s how I have felt ever since. UCSF has the people; it has the leadership. The

leadership instills a sense of concern, caring and professionalism in every doctor, resident, nurse, caregiver, receptionist and counselor. This kind of spirit, together with the leading edge medical treatment found here, gives patients a better chance at success. We all have a real jewel here. We should cherish it.

WHY I GIVE TO UCSF: I want to do whatever I can to help clinicians and researchers find better ways to diagnose, some way to early detect, possibly even a way to genetic map, better ways to treat, and ultimately the way to cure this disease. Different people will be able to do different things, and at different levels. But, if we all do something, we can score some victories in the fight against pancreatic cancer, the fourth leading cause of cancer death in America.

FROM THE DIRECTORContinued from front page

“Everyone I have come in contact with at UCSF I consider a friend. They are brilliant people who are also very caring, concerned and thoughtful.” – Marilyn Amsden

donor snapshots

Marilyn Amsden and her son Dan

Because there is currently no cure, receiving a diagnosis of pancreas cancer can be overwhelming for

patients and their families. It’s the job of Anna Ong to help allay their fears by educating them about the disease and their treatment options. As one of two nurses dedicated to pancreas cancer research at the UCSF Medical Center at Mount Zion, Ong also coordinates clinical trials for novel cancer treatments and regimens, and explains to patients what the treatment will do for and to them.

This type of nursing is unique in that Ong is dedicated specifically to patients of the pancreas cancer research program, which gives her the ability to focus solely on these patients. “This specialized care makes a big difference to patients,” says Ong. In addition, every staff member is familiar with each patient’s treatment regimen, diet and medical history. This continuity of care allows the patients to feel that UCSF is a medical family.

“We give patients our direct number, email address and pagers,” Ong says, “so that we’re available to them when they need us. We can talk to them on a day-to-day basis to see how they’re tolerating their regimen and to help them manage their side effects.”

The close relationship Ong forms with her patients lets her monitor and quickly become aware of any problematic clinical symptoms and emotional stress that occur due to the illness or treatment. If problems arise, Ong can refer the patient to a number of groups and resources within the hospital. Because UCSF is

multidisciplinary, she and the research team work closely with medical center dieticians, psychologists, palliative care physicians and social workers to alleviate patient symptoms and to improve their quality of care and quality of life.

“It’s not only about prolonging the patients’ lives, but also about what we do for them with the time they have left,” says Ong. “We manage their symptoms, making sure that they can do the things that they enjoy.

The research is about finding an effective and tolerable treatment so patients can enjoy the people and things in life that make them happy.”

Ong began her career with California Pacific Medical Center in medical-surgical nursing, practicing her skills at the bedside. She later moved into the transitional intensive care unit and an administrative position, but found that she “really missed the hands-on and working directly with the patient.” She joined the pancreas cancer research team in October 2009 and today says she feels most gratified knowing that she makes a difference in a patient’s journey and fight against pancreas cancer.

Pancreas cancer research nurse Anna Ong checks in with patient Jane Bailowitz.

clinical careShe’s Got Your Back

“It’s not only about prolonging the patients’ lives, but also about what we do for them with the time they have left.”– Anna Ong

A poor survival rate remains a deva- stating fact for pancreas cancer patients, their families and their

physicians. One barrier to advancing diagnosis and treatment is a paucity of tissue to study. Tissue samples can hold the key to discovering early detection tools, biomarkers and more effective therapies.

As part of her longstanding effort to tear down this barrier, Margaret Tempero, MD, director of the Pancreas Center, is spearheading the innovative Clinically Annotated Pancreas Tumor Repository (CAPTuRe) project at UCSF. CAPTuRe will maximize available tissue and serve as a central clearinghouse where researchers can find rigorously vetted information to accelerate their efforts.

A Difficult ProblemShortage of pancreas cancer tissue is a complicated problem. By the time most patients receive a diagnosis, they will not benefit from surgery. “Those who can benefit are only a subset of patients and the actual epithelial component of any resected tumor – what we can use for study – is typically small,” says Tempero.

Other tissue that can help researchers – blood and serum or biopsied tumors from non-surgical patients – can require asking patients to participate in procedures that may or may not be medically necessary. And even when tissue is available, creating standardized processes for prioritizing its use, conducting scientific analyses, and quickly disseminating findings is an ongoing challenge.

How It Works The CAPTuRe project brings together four related research efforts under one virtual roof.

Capturing Tissue Advances Diagnosis and Treatment

The first is the actual tissue bank. When oncologists and surgeons identify a patient who can benefit from surgery, CAPTuRe will acquire and store the resected tumors using standard operating protocols, including freezing the samples or preserving them in formalin-fixed, paraffin-embedded blocks. Blood and serum from these patients, as well as from others who are participating in clinical trials, also will populate the tissue bank.

A second piece will be molecular analyses on the tissue that include gene sequencing, mutation character-ization and comparative genomic hybridization arrays – a methodology that helps scientists get a more comprehensive picture of genetic variations associated with cancers. “Patients benefit because these analyses can inform more targeted therapeutic decisions,” says Tempero.

In a third piece, research teams led by Rosemary Akhurst, PhD, and Byron Hann, MD, PhD, will implant fresh tissue in genetically engineered mice. There, cell lines can thrive and be observed with advanced imaging techniques. The insights gleaned can support the development and

translation of innovative cancer therapies.

Finally, by carefully tracking patient outcomes and linking them to the samples and profiles, CAPTuRe addresses a weakness in many similar efforts. “It’s labor-intensive because our patients get care at many sites,” says Tempero. “But it’s a level of insight we are determined to add.”

Beyond UCSFTempero, who will assume the Rombauer Family Distinguished Professorship in Pancreas Cancer Clinical and Translational Science in July, says the implementation of CAPTuRe will enable UCSF to sync with a similar nationwide effort that she leads. CAPTuRe is already partnering with UC Santa Cruz, which has a genome browser that supports national and international efforts.

“That’s the portal through which information would become publicly available,” says Tempero. “I’m excited about this project, because it should enable us to make the most use of every sample and accelerate our research efforts.”

The preclinical therapeutic core team (from left):

Byron Hann, Donghui Wang, Paul Phojanakong, Rosemary Akhurst,

Don Hom

clinical research

Candidate identified for resection

Tumor tissue collected Molecular

analyses

Cells grown in mice

Fragment of a patient-derived pancreas tumor grown in a mouse host in Byron Hann’s laboratory.

This tumor retains cardinal features that characterize the human disease.

Upgrading the Arsenal“This is a war, and if it means stealing tactics that have been successful in other cancers, then we’re happy to fight dirty,”says medical oncologist Eric Collisson, MD, of his and others’ efforts to improve pancreas cancer treatment.

Collisson completed undergraduate studies at UC Berkeley, medical school at UCLA, internal medicine training at Stanford University, a medical oncology fellowship at UCSF, and post-doctoral studies on the genomics of pancreas cancer at Lawrence Berkeley National Labs. Now, he is vigorously pursuing multiple avenues

to improve treatment for pancreatic ductal adenocarcinoma (PDA).

At the UCSF Division of Hematology/Oncology, where Collisson divides his time between the clinic and the laboratory, his research proceeds along two complementary paths.

One path is rooted in studies that have shown patients respond differently to treatment at least partly because of molecular differences in their tumors. With that in mind, Collisson and his colleagues have defined three PDA tumor subtypes and demonstrated that they respond differently to therapies. The team also has identified markers associated with these subtypes, which physicians could eventually use to stratify patients for treatment.

Collisson’s second research path is where the concept of “stealing tactics” is particularly applicable. He is a member of lung and colon cancer teams that are helping to create the Cancer Genome Atlas at the National Cancer Institute –

an effort that annotates the genomic profiles of hundreds of cancers. He says, “I am trying to beg, borrow and steal genomic correlations from other diseases for my work on pancreas cancer.”

Known as “cross tumor genomic analysis,” this approach is gaining increased scientific interest. “We’ve studied many more cancers in general than we will ever study pancreas cancers,” Collisson explains. “An emerging concept is to leverage the power of the large numbers and deep annotation to learn across many cancers how to more effectively treat specific cancers.”

That approach makes sense to Collisson, the clinician. He points to the discovery that a rare form of lymphoma shares a genetic abnormality with 10 percent of lung cancers. That knowledge led to a drug that now prolongs the life of patients with each type of otherwise unrelated forms of cancer,

Collisson hopes to make similar cross tumor genomic discoveries for pancreas cancer. “I treat a lot of colon, lung and pancreas cancer,” he says. “These cancers share the prevalence of a specific mutation, so many of us are hoping to create molecular oncology clinics where we organize patient visits and treatment around a treatable genomic event instead of around a specific disease per se. We still have to be good doctors and treat all aspects of the disease, but understanding the genetic pathways operative in a tumor is increasingly important if we are to move toward more effective therapies.”

young investigator

“An emerging concept is to leverage the power of the large numbers and deep annotation

to learn across many cancers how to more effectively treat specific cancers.”

– Eric Collisson

Molecularanalyses

Cells grown in mice

Living mice with light emitting pancreas cancer. The pattern of light emission differs between

early- and late-stage cancer cells.

For more information on the Pancreas Cancer Program, contact Pam Elmore: 415/353-7390; pelmore@medicine.ucsf.edu

How You Can Help – Participate in one of these fundraisers to benefit pancreas cancer research at UCSF

Managing Editor: Kate Volkman

Writers: Andrea Sajuthi, Andrew Schwartz, Kate Volkman

Photography: Noah Berger, Stuart Brinin, Elisabeth Fall

Design: Laura Myers Design

© 2012 The Regents of the University of California

Don Ritchie 5K Run/WalkMonday, May 28 / College of Marin / Kentfield, CAThis Memorial Day 5K run/walk is certified, flat and fast, and concludes with a dramatic finish in the College of Marin Stadium. Organized by Jane Ritchie and Dave Ripp, it is a fundraiser for pancreas cancer research at UCSF and is dedicated to the memory of Ritchie’s husband, Don. Don was a longtime Tamalpa Runner and Marin County educator who died of pancreas cancer in 2009.

pancreas cancer news

Walk 4 Pancreatic CancerSaturday, May 12 / Santa Clara, CAThis 10K walk takes place around the beautiful Santa Clara University campus. Organized by Arlene Mariani, this fantastic day of friendship and fun welcomes runners, strollers and family members of all ages. Every penny raised will be donated to pancreas cancer research at UCSF.

Register at www.walk4pancreaticcancer.com Register at www.marinraces.com

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