A gift to the Department of Surgery helps our physicians and scientists find new treatments and cures for serious diseases.
Dr. Eric Nakakura is a cancer surgeon who specializes in tumors of the pancreas, bile ducts, liver, and gastrointestinal tract. He also treats soft tissue sarcomas, including tumors of the retroperitoneum, trunk and extremities. At the UCSF Helen Diller Family Comprehensive Cancer Center, he participates in the management of complex gastrointestinal tract cancers, soft tissue sarcomas and gastrointestinal neuroendocrine tumors, including carcinoid and islet cell tumors.
Dr. Nakakura earned a medical degree at Stanford Medical School and a doctorate degree in cellular and molecular medicine at the Johns Hopkins University. He completed a residency in general surgery at the Johns Hopkins Medical Institutions and was a specialist registrar in surgery at the John Radcliffe Hospital in Oxford, England. He completed a fellowship in surgical oncology at the Johns Hopkins Medical Institutions. Dr. Nakakura, an assistant professor of surgery at UCSF, studies endocrine differentiation in gut and gastrointestinal tumors and cancer stem cells. Highly respected by his peers, Dr. Nakakura was named to the list of U.S. News "America's Top Doctors," a distinction reserved for the top 1% of physicians in the nation for a given specialty.
Dr. Nakakura was recently awarded the 2012 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research based on the foundation's belief that his research would "significantly increase the understanding of pancreatic neuroendocrine tumors."he 2012 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research application you submitted was approved for funding. This decision was based on the relevance of your application to the mission of both organizations and a belief that your project will add significantly to the understanding of pancreatic neuroendocrine tumors.
Neuroendocrine (NE) tumors of the gastrointestinal (GI) tract frequently metastasize. Surgery is often not possible for patients with advanced disease, and current therapies are ineffective for shrinking tumors and durable palliation of debilitating hormonally-mediated symptoms. Dr. Nakakura and his colleagues have as a long-term goal is to elucidate the transcriptional and signaling events critical to the pathogenesis of NE tumors of the GI tract, which can identify novel targets for diagnosis and treatment.
Developmental biology provides important clues and Dr. Nakakura and his fellow scientists have found that the same transcription factors and signaling pathways that function in the normal development of endocrine cells throughout the body also act to regulate NE tumor hormone production and growth, as well as metastasis. Their findings that conserved pathways of NE differentiation function in cancer have also shed important insight into normal gut endocrine cell development.
The group has ongoing studies to evaluate the role of proendocrine transcription factors and signaling pathways in normal and neoplastic gut using in vivo and in vitro model systems. In addition, Dr. Nakakura has leveraged his unique skills as a surgical oncologist to develop novel NE and other gastrointestinal cancer xenografts and cell lines, invaluable resources to the entire research community.
This work is complemented by studies of human GI NE tumors and of clinical studies of patients suffering from this disease. Dr. Nakakura is also active in bench-to-bedside (translational) studies aimed at earlier detection of NE tumors at at time when there is still the possibility of surgical resection. He is also investigating new and novel therapies for patients with advanced disease who have inoperable tumors.
Eric Nakakura, M.D., Ph.D. has been awarded the 2012 Caring for Carcinoid Foundation-AACR Grant for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research. Dr. Nakakura will receive $250,000 over two years to understand why some patients develop resistance to mTOR inhibiting drugs like everolimus. In particular, he will focus on INK128, a new mTOR inhibitor to see if it can overcome this resistance in mouse models of pancreatic neuroendocrine cancer. He will also evaluate the utility of (68)GA-DOTATOC PET-CT to monitor tumor response to mTOR inhibiting therapies like everolimus and INK128.
In its most recent survey, U.S. News in collaboration with Castle Connolly Medical Ltd. listed twenty-five (25) surgeons in the UCSF Department of Surgery, nearly one-third (1/3) of the clinical faculty, on the list of U.S. News "Top Doctors". The list, compiled from the opinion of colleagues, denotes the top 10% of physicians within a region practicing a given specialty. Fifteen of the 25 department surgeons were also named by their peers to the list of America's Top Doctors (ATD), a distinction reserved for the top 1% of physicians in the nation for that specialty. The listings are published online at U.S. News. The group rankings are intended to guide patients in selecting a doctor and physicians in making specialty referrals.
Then post-graduate student Eric Nakakura, M.D., Ph.D., working in the lab of Johns' Hopkins cancer biologist Barry Nelkin, was struck by how the migration of neurological cells to form the developing brain bore an uncanny similarly to the inexorable migration of invasive cells to distant sites in cancer metastasis. Today, the insight of Dr. Nakakura, now an Assistant Professor in Division of General Surgery and Surgical Oncology Program, forged with postdoctoral fellow Chris Strock, has led to the discovery that an enzyme known as CDK5 and a pathway, RAL, play key roles in the ability of cells to migrate, form cancers and metastasize. This finding may be significant in the development of targeted biological agents against pancreatic cancer, one of the most lethal malignancies among solid organ tumors.
UCSF researchers, led by Doug Hanahan, Ph.D. (left), have identified collections of tiny molecules known as microRNAs that affect distinct processes critical for cancer progression. The findings help elucidate the important regulatory function of microRNAs in tumor biology. Eric Nakakura, M.D., Ph.D. (right), a surgeon-scientist who treats patients with challenging pancreatic neuroendocrine tumors, was on the team that validated the findings, which were based on an exquisite mouse model of pancreatic neuroendocrine tumors. Many of the same altered microRNAs in were found to be present in human pancreatic neuroendocrine tumors. This represents a major advance in our understanding of pancreatic neuroendocrine tumor biology, one that might be exploited to better treat patients.
"Surgery for pancreas cancer is long and demanding, and surgeons must be practiced to consistently perform it well. Pancreas cancer surgery outcomes are better at high-volume, major medical centers such as UCSF, where surgeons can specialize - perfecting and maintaining skills and deepening their experience and judgment." UCSF surgeons Kimberly Kirkwood, M.D., and Eric Nakakura, M.D., Ph.D., achieve outstanding outcomes for standard procedures and also perform operations rarely offered elsewhere for select patients who would otherwise not meet criteria for surgical treatment.
"Soft tissue sarcomas are extraordinarily heterogeneous, so experience is particularly important when deciding among treatment options," says medical oncologist Thierry M. Jahan, M.D. (pictured right). At UCSF, referring physicians typically send patients with painful, growing soft tissue masses to orthopedic surgeon Richard J. O'Donnell, M.D., and general surgeon Eric K. Nakakura, M.D., Ph.D, (pictured left). If their initial examination convinces them that there is a sarcoma concern, they move on to a staging workup that includes various imaging modalities and, eventually, either a needle or incisional biopsy...."