Unexpected Activity of Two Enzymes Helps Explain Why Liver Cancer Drugs Fail

Overturning previous assumptions, study also provides new, more realistic model for liver cancer research and drug development —

Some cancers are caused by loss of enzymes that should keep cell growth in check. On the flip side, some are caused by over-activation of enzymes that enhance cell growth. Yet drugs that inhibit the overactive enzymes have failed to work against liver cancer. In mouse models, researchers at University of California San Diego School of Medicine have discovered a potential reason — counterintuitively, lack of both types of these enzymes can lead to liver disease and cancer. In human liver tumor samples, they also found that deficiencies in these two enzymes, called Shp2 and Pten, are associated with poor prognosis.

The study, published December 13 by Cell Reports, provides a new understanding of how liver cancer develops, a new therapeutic approach and new mouse model for studying the disease. … Read the Full Story from the UC San Diego Newsroom


Rohit Loomba, MD

Rohit Loomba, MD

The study team includes Rohit Loomba, MD, MHSc, Director of the NAFLD Research Center and Director of Hepatology in the Division of Gastroenterology, Department of Medicine at UC San Diego. Dr. Loomba is Professor of Medicine (with tenure) and Vice Chief, Division of Gastroenterology.

Dr. Loomba is also Adjunct Professor, Division of Epidemiology, Department of Family Medicine and Public Health.

Researchers Identify Liver Cancer Progenitor Cells Before Tumors Become Visible

For the first time, researchers at the University of California, San Diego School of Medicine have isolated and characterized the progenitor cells that eventually give rise to malignant hepatocellular carcinoma (HCC) tumors – the most common form of liver cancer. The researchers found ways to identify and isolate the HCC progenitor cells (HcPC) long before actual tumors were apparent. … Read the full story from the UC San Diego News Center

Clinical Trial Evaluates Engineered Smallpox Vaccine as Potential Liver Cancer Killer

As part of a multicenter clinical trial, researchers at University of California, San Diego School of Medicine are evaluating Pexa-Vec (JX-594) to slow the progression of hepatocellular carcinoma (HCC) or liver cancer. Pexa-Vec is a genetically engineered virus that is used in the smallpox vaccine.. … Read the full story from the UCSD Newsroom


Dr. Tony ReidPhysician-scientist Tony Reid, MD, PhD, is principal investigator of this clinical trial of Pexa-Vec (JX-594) at UC San Diego, which is one of 42 sites participating in the study.

Reid is professor of medicine and medical oncologist in the Gastrointestinal Cancer Unit of the UCSD Moores Cancer Center. He conducts research in the center’s Solid Tumor Therapeutics Program.

For more information about the Pexa-Vec (known as TRAVERSE) clinical trial, call 858-822-5354 or visit http://traversetrial.com.

Profile: Dr. William Sandborn, New Chief of Gastroenterology

DrWilliamSandborn_160x200“We’re open for business,” smiled Dr. William Sandborn, UC San Diego’s new Chief of Gastroenterology.

He has launched his clinics and plunged into his administrative roles. He is assembling teams to conduct clinical trials of potential treatments for inflammatory bowel disease (IBD), in which he is an internationally esteemed clinician and researcher.

William J. Sandborn Jr., MD, comes to UC San Diego from the Mayo Clinic in Rochester, Minnesota, where he was Dorothy A. Adair Professor of Medicine, vice chair of the Mayo Clinic Division of Gastroenterology and Hepatology, and associate dean of research for Intellectual Property and Industry Relations.

He sees the possibilities here as limitless.

“Gastroenterology at UC San Diego is at the beginning of a period of great change that I think will be very positive,” he said, “with the expansion of the clinical enterprise over the next five years that includes a dramatic extension of UC San Diego Health System’s La Jolla campus.”

“It is a really exciting time to be here,” he said.


“We’re coming together across departments to create service lines
to address the unmet needs of our patients.”


Patient Care: Growing to Meet More Needs

Gastroenterology is significantly expanding its patient care capabilities by drawing on UC San Diego’s institutional strengths and establishing key new efforts in transplantation, liver cancer, non-alcoholic steatohepatitis, and viral hepatitis, Sandborn said.

“We have fabulous multidisciplinary teams,” he said. “We’re coming together across departments to create service lines to address the unmet needs of our patients.”

There are strong partnerships with the Departments of Surgery and Radiology, among others. The new Center for Hepatobiliary Disease and Abdominal Transplantation (CHAT), co-directed by Robert G. Gish, MD, and surgical professor Alan Hemming, MD, MSc, is one of many programs that will be important, Sandborn said.

Dr. Gish, an internationally respected liver specialist who joined the Gastroenterology faculty late last year, is the new chief of clinical hepatology and director of the Liver Center.

Other major clinical efforts include the Gastrointestinal Endoscopy program, headed by Dr. Tom Savides, and Sandborn’s own clinics for inflammatory bowel disease (IBD).

Sandborn will lead UC San Diego Health System’s Inflammatory Bowel Disease Center, a new multidisciplinary clinical effort designed to serve the estimated 15,000 individuals in San Diego County who suffer from IBD.


New UCSD Inflammatory Bowel Disease Center
is a collaboration with the Department of Surgery


IBD is the collective term for inflammatory conditions of the colon and small intestine. The most common types of IBD are ulcerative colitis and Crohn’s disease. Although there is a genetic predisposition to developing IBD, there is no known cause or certain cure. Treatment requires lifelong medical care for many sufferers and involves the suppression of the body’s abnormal inflammatory response. Ulcerative colitis may be surgically curable as it is limited to the colon. Although Crohn’s disease is not curable, some patients may also benefit from surgery.

According to the Greater San Diego and Desert Area Chapter of the Crohn’s and Colitis Foundation of America, the local IBD prevalence rate is approximately one in 200 people. The actual number of those affected could be higher, as the symptoms of IBD often overlap with those of other disorders.

UC San Diego Health System’s IBD Center is a collaboration with surgeons Mark Talamini, MD (Chief of the Department of Surgery), Sonia Ramamoorthy, MD, and Lisa McLemore, MD, in the Division of Colorectal Surgery. In addition to Dr. Sandborn, the Center’s gastroenterologists include Michael Docherty, MD, and Derek Patel, MD, who have advanced subspecialty training in IBD.

Surgeon’s Son Planned to Follow in Father’s Footsteps

Sandborn received his gastroenterology fellowship training at the Mayo Clinic after completing his medical school training, internship, and internal medicine residency at Loma Linda University in Loma Linda, California.

He joined the faculty of the Division of Gastroenterology and Hepatology at the Mayo Clinic when he completed his fellowship there in 1993.


As a youth, he observed surgeries, joined his father on rounds


The son of a general surgeon, Sandborn had the opportunity to see the practice of medicine up close when he was in his youth. He observed surgeries and went along on his father’s rounds from time to time, and he initially intended to become a surgeon himself.

During the gastroenterology rotation in his internal medicine residency training at Loma Linda University, he discovered a deep interest in gastroenterology.

He chose the subspecialty for its blend of diagnosis, pharmacology, and patient care; he enjoys both the technical side and the human side of his work, he said.

Because inflammatory bowel disease tends to occur early in life, many of his patients are young when they first come to see him. They grow up, enter college, start their families, and start their careers as he manages their treatment.

“I get to see them go through the years,” Sandborn said.

He often becomes his patients’ main doctor, serving in a sense as a classic primary care physician but with the specificity and cutting-edge technology of gastroenterology practice.

“In IBD,” he said, “we suppress the disease chronically, and we are able to achieve increasingly good outcomes in our patients. We don’t cure because we don’t yet know the causes of the disorders.”


Through clinical trials, Sandborn works to make new IBD treatments available


Because he is a clinician who is also a longtime clinical trials researcher, he sometimes has the chance to see his own patients benefit from drug treatments he has been involved in developing. “That is a privilege,” he said, “that not very many people have.”

And, as it turns out, he practices in a field where internal medicine and surgery overlap. “IBD patients sometimes need surgical care as well as management with pharmacological treatments,” he said. “I get to do a little bit of everything.”

UCSD: “Fantastic Research Capabilities and a Wealth of Experience”

Sandborn is widely respected for his research in the pharmacological treatment of IBD. He has designed and directed many clinical trials of current and potential future IBD treatments and has published more than 350 scholarly articles in major journals. In 2010, he was honored with the Scientific Achievement in IBD Clinical Research Award from the Crohn’s and Colitis Foundation of America.

He sees excellent research opportunities here at UC San Diego.

“There are fantastic research capabilities and a wealth of experience in the Department of Medicine and the other departments and schools as well as in the research institutes and the biotechnology companies in the surrounding area,” he said.


Sandborn sees excellent research opportunities here at UC San Diego


He pointed to recent major developments in research at UC San Diego, among them the Clinical and Translational Science Award to Dr. Gary Firestein for the Clinical and Translational Research Institute.

Sandborn expects to begin his own clinical trials here in the second quarter of this year. He will be studying several biologic therapies designed to intervene in the chronic inflammation of IBD by blocking integrins and thereby preventing white blood cells from migrating to inflamed tissues in the intestinal wall.

He will also study specific monoclonal antibodies as potential treatments for Crohn’s disease. These compounds target the T-cell proinflammatory cytokines interleukin (IL)-12 and IL-23.

Continuing a Tradition of Leadership

As Gastroenterology chief here, Sandborn hopes to be a leader in the tradition of his mentors at Mayo Clinic and elsewhere. “Drs. Nick LaRusso, Keith Lindor and Greg Gores are excellent, inspiring, visionary leaders,” he said, naming three successive chiefs of the Division of Gastroenterology and Hepatology at the Mayo Clinic.

Two others played particularly significant roles in shaping his career. “Drs. Stephan Targan at Cedars-Sinai Medical Center in Los Angeles and Stephen B. Hanauer of the University of Chicago had a big impact on me, even though we were not at the same institution,” he said.

In recognition for his own efforts as a mentor, Sandborn received the Outstanding Mentor Award from the Department of Medicine at the Mayo Clinic in 2010.

Sandborn is an elected Fellow of the American College of Physicians (1996), the American College of Gastroenterology (1998), and the American Gastroenterological Association (2008).

He has held numerous positions on extramural committees, the most recent including the Immunology, Microbiology, and Inflammatory Bowel Disease Section of the American Gastroenterology Association (chair, 2006-2008); the AGA Institute Future Trends Committee (member, 2007-2009); the Inflammatory Bowel Disease Working Group of the National Commission on Digestive Diseases (member, 2007); and the International Organization of Inflammatory Bowel Disease (chair, 2008-2010).

About Sandborn’s Mentors

Nicholas F. LaRusso, MD, is Professor of Biochemistry/Molecular Biology and Professor of Medicine and Keith D. Lindor, MD, is Professor of Medicine in the Department of Medicine at the Mayo Clinic. Gregory J. Gores, MD, is Reuben R. Eisenberg Endowed Professor in Gastroenterology and Hepatology, Professor of Medicine, and chair of the Division of Gastroenterology and Hepatology at the Mayo Clinic.

Stephan Targan, MD, directs the Inflammatory Bowel Disease Center and the Division of Gastroenterology at Cedars-Sinai Medical Center. He is Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and holds the Feintech Family Chair in Inflammatory Bowel Disease at Cedars-Sinai.

Stephen B. Hanauer, MD, is Joseph B. Kirsner Professor of Medicine, Professor of Clinical Pharmacology and Chief, Section of Gastroenterology and Nutrition at the University of Chicago.