eBriefing

Pancreatic Cancer: Translation of New Ideas

Pancreatic Cancer
Reported by
Megan Stephan

Posted December 12, 2012

Overview

Pancreatic cancer is a leading cause of cancer death in the United States and is poised to become even more significant over the next two decades. This cancer usually goes undetected until it has reached an advanced stage, and patients face dismal prognoses due to the lack of effective therapies. However, recent years have seen the development of new molecular tools and animal models for investigating the mechanisms of pancreatic cancer initiation and development, which have led to new insights into potential therapeutic targets. This symposium, Pancreatic Cancer: Translation of New Ideas, presented on October 12, 2012, by the Cancer and Signaling Discussion Group at the New York Academy of Sciences, brought together scientists, translational researchers, and clinical investigators to explore multiple promising new approaches to treating this deadly disease.

Use the tabs above to find a meeting report and multimedia from this event.

 

Presentations available from:
Dafna Bar-Sagi, PhD (New York University Langone Medical Center)
Adrienne D. Cox, PhD (University of North Carolina at Chapel Hill)
Jeffrey M. Hardacre, MD (University Hospitals Case Medical Center)
Alec C. Kimmelman, MD, PhD (Dana Farber Cancer Institute, Harvard Medical School)
David A. Tuveson, MD, PhD (Cold Spring Harbor Laboratory)


Mission Partner support for the Frontiers of Science program provided by: Pfizer

Websites

American Cancer Society. Cancer Facts & Figures 2012. Atlanta, GA; 2012. Annual summary of cancer statistics from the American Cancer Society. Features a special section on cancers with increasing rates, including pancreatic cancer.

The Human Gene Compendium. Gene Cards: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. Weizmann Institute of Science; 2012. Kras gene description and links to further resources.

Cell Signaling Technology. The Human Kinome. 2012. Interactive map showing evolutionary relationships between human protein kinases.

National Cancer Institute at the National Institutes of Health. Pancreatic Cancer. Information for both professionals and patients on the prevention, diagnosis, and treatment of pancreatic cancer, including clinical trial listings and recent news.

NewLink Genetics. 2011. Company that is developing algenpantucel-L.

Pancreatic Cancer Action Network. 2012. Patient organization providing information and support for individuals with pancreatic cancer.


Journal Articles

Ahearn IM, Haigis K, Bar-Sagi D, et al. Regulating the regulator: post-translational modification of RAS. Nat Rev Mol Cell Biol. 2012;13:39-51.

Campbell PM, Boufaied N, Fiordalisi JJ, et al. TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signaling. J Mol Signal. 2010 Nov 2;5:18.

Cook N, Jodrell DI, Tuveson DA. Predictive in vivo animal models and translation to clinical trials. Drug Discov Today. 2012;17:253-60.

Cox AD, Der CJ. The raf inhibitor paradox: unexpected consequences of targeted drugs. Cancer Cell. 2012;17:221-3.

Cox AD, Der CJ. The RAF inhibitor paradox revisited. Cancer Cell. 2012;21:147-9.

Cox AD, Olive KP. Silencing the killers: paracrine immune suppression in pancreatic cancer. Cancer Cell. 2012;21:715-6.

Eheman C, Henley SJ, Ballard-Barbash R, et. al. Annual Report to the Nation on the Status of Cancer, 1975-2008, Featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012 May 1;118(9):2338-66.

Feig C, Gopinathan A, Neesse A, et al. The pancreas cancer microenvironment. Clin Cancer Res. 2012;18:4266-76.

Frese KK, Neesse A, Cook N, et al. nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov. 2012;2:260-9.

Hardacre JM. Is there a learning curve for pancreaticoduodenectomy after fellowship training? HPB Surg. 2010;2010:230287.

Hardacre JM, Simo K, McGee MF, et al. Pancreatic resection in octogenarians. J Surg Res. 2009;156:129-32.

Kimmelman AC. The dynamic nature of autophagy in cancer. Genes Dev. 2009;25:1999-2010.

Kimple RJ, Vaseva AV, Cox AD, et al. Radiosensitization of epidermal growth factor receptor/HER2-positive pancreatic cancer is mediated by inhibition of Akt independent of ras mutational status. Clin Cancer Res. 2010;16:912-23.

Jacobetz MA, Chan DS, Neesse A, et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut. 2012 Mar 30.

Lee KE,Bar-Sagi D. Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. Cancer Cell. 2010;18:448-58.

Mallen-St Clair J, Soydaner-Azeloglu R, Lee KE, et al. EZH2 couples pancreatic regeneration to neoplastic progression. Genes Dev. 2012;26:439-44.

Neesse A, Michl P, Frese KK, et al. Stromal biology and therapy in pancreatic cancer. Gut. 2011;60:861-8.

Nikfarjam M, Staveley-O'Carroll KF, Kimchi ET, et al. Pancreaticoduodenectomy in patients with a history of Roux-en Y gastric bypass surgery. JOP. 2009;10:169-73.

Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer. 2011;11:761-74.

Pylayeva-Gupta Y, Lee KE, Hajdu CH, et al. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21:836-47.

Mancias JD, Kimmelman AC. Targeting autophagy addiction in cancer. Oncotarget. 2011;2:1302-6.

Yang S, Kimmelman AC. A critical role for autophagy in pancreatic cancer. Autophagy. 2011;7:912-3.

Yang S, Wang X, Contino G, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011;25:717-29.

Ying H, Kimmelman AC, Lyssiotis CA, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656-70.

Organizers

Kenneth P. Olive, PhD

Columbia University Medical Center
e-mail | website | publications

Kenneth P. Olive began his doctoral studies in 1998 with Tyler Jacks at the MIT Center for Cancer Research, investigating the neomorphic effects of mutant p53 in a mouse model of Li-Fraumeni Syndrome. While at MIT, he also helped develop a conditional mutant model of advanced lung adenocarcinoma. After graduating in 2005, Olive began a postdoctoral fellowship in the laboratory of David Tuveson at the University of Pennsylvania, later moving with the lab to the University of Cambridge. There he built a translational research facility for studying novel anticancer therapeutics in genetically engineered mouse models of pancreatic cancer. His studies into chemoresistance and the effects of Hh pathway inhibitors on drug delivery in pancreatic cancer were published in Science in 2009 and have led to multiple clinical trials to evaluate the approach in patients with metastatic pancreatic cancer. In 2010, Olive joined the faculty of the Columbia University Herbert Irving Comprehensive Cancer Center, where he has established a laboratory dedicated to translational science and experimental therapeutics in pancreatic ductal adenocarcinoma.

George Zavoico, PhD

MLV
e-mail | website | publications

George Zavoico is managing director of research and a senior equity research analyst at MLV & Co., a boutique investment bank and institutional broker-dealer based in New York. He has over six years of experience as a life sciences analyst, writing on publicly traded equities. Prior to MLV, he was an equity analyst with Westport Capital Markets and Cantor Fitzgerald. Prior to working as an analyst, Zavoico established his own consulting company, serving the biotech and pharmaceutical industries by providing competitive intelligence and marketing research, due diligence services, and guidance in regulatory affairs. He also wrote extensively on healthcare and the biotech and pharmaceutical industries for periodicals targeting the general public and industry executives. Zavoico began his career as a senior research scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals, Inc. and T Cell Sciences, Inc. (now Celldex Therapeutics, Inc.). He holds a PhD in Physiology from the University of Virginia and has held post-doctoral positions at the University of Connecticut Health Sciences Center, Brigham and Women's Hospital, and Harvard Medical School.

Jennifer Henry, PhD

The New York Academy of Sciences
e-mail

Jennifer Henry is the director of Life Sciences at the New York Academy of Sciences. Henry joined the Academy in 2009, before which she was a publishing manager in the Academic Journals division at Nature Publishing Group. She also has eight years of direct editorial experience as editor of Functional Plant Biology for CSIRO Publishing in Australia. She received her PhD in plant molecular biology from the University of Melbourne, specializing in the genetic engineering of transgenic crops. As director of Life Sciences, she is responsible for developing scientific symposia across a range of life sciences, including biochemical pharmacology, neuroscience, systems biology, genome integrity, infectious diseases and microbiology. She also generates alliances with organizations interested in developing programmatic content.


Keynote Speaker

Dafna Bar-Sagi, PhD

New York University Langone Medical Center
e-mail | website | publications

Dafna Bar-Sagi has been the senior vice president and vice dean for science and the chief scientific officer of NYU Langone Medical Center since the summer of 2011. She is also a professor of biochemistry. One of the country's leading cancer biologists, Bar-Sagi is widely known for elucidating cellular pathways involved in controlling cell growth. She has published more than 100 peer-reviewed research papers in leading journals on the molecular mechanisms underlying tumor development, devoting considerable research to RAS proteins, essential control elements of molecular machineries that drive the neoplastic process in many human cancers. Prior to joining the NYU Langone Medical Center in 2006 as chair of the Department of Biochemistry, Bar-Sagi headed the Department of Molecular Genetics and Microbiology at the State University of New York (SUNY) at Stony Brook. She earned her undergraduate and master's degrees from Bar-Ilan University, Israel, and her PhD from SUNY at Stony Brook. She has been a member of many scientific advisory boards including Starr Cancer Consortium, Pancreatic Cancer Action Network, and Abramson Family Cancer Research Institute and has served on the editorial boards of multiple journals including Cancer Cell, Oncogene, and Molecular and Cellular Biology.


Speakers

Adrienne D. Cox, PhD

University of North Carolina at Chapel Hill
e-mail | website | publications

Adrienne D. Cox is an associate professor of pharmacology and radiation oncology at the University of North Carolina at Chapel Hill. She was a National Merit Scholar at Pomona College, a founding student of the interdisciplinary Biomedical Sciences PhD program, and a National Science Foundation Fellow at Eastern Virginia Medical School. She completed her postdoctoral studies with Channing Der at what is now the Sanford-Burnham Institute. Cox has extensive experience in basic and translational studies of Ras family small GTPases. Since the earliest studies of the mechanisms of action of farnesyltransferase inhibitors, she has helped to elucidate the role and importance of posttranslational modifications such as isoprenoid lipids and phosphorylation to the membrane targeting events that drive Ras family signaling specificity, and emphasized the importance of isoform differences in promoting context-dependent oncogenesis. Her focus on molecular therapeutics of pancreatic cancer is driven by these findings. A member of the Lineberger Comprehensive Cancer Center, Cox is currently the chief of the Division of Cancer Research in the Department of Radiation Oncology.

Jeffrey M. Hardacre, MD

University Hospitals Case Medical Center
e-mail | website | publications

Jeffrey M. Hardacre received his MD from Duke University School of Medicine, where he was a Howard Hughes Medical Student Research Training Fellow. He completed his surgical training at the Johns Hopkins Hospital. In 2004 he joined the Department of Surgery at University Hospitals Case Medical Center and Case Western Reserve University School of Medicine in Cleveland. Currently, he is an associate professor of surgery and the section head of pancreatic surgery at University Hospitals Seidman Cancer Center.

Alec C. Kimmelman, MD, PhD

Dana Farber Cancer Institute, Harvard Medical School
e-mail | website | publications

Alec C. Kimmelman is an assistant professor of radiation oncology at the Dana-Farber Cancer Institute at Harvard Medical School. He completed his undergraduate education at Cornell University and received his MD/PhD from the Mount Sinai School of Medicine. He completed residency training at the Harvard Radiation Oncology Program and performed his postdoctoral studies in the laboratory of Ronald A. DePinho at the Dana-Farber Cancer Institute, where he identified novel genes that are important in the invasive and metastatic phenotype of pancreatic cancer. Kimmelman's lab is focused on pancreatic cancer, and their recent work involves the study of the deregulation of metabolic pathways in the disease and its relation to therapeutic resistance. These studies have identified that pancreatic cancers are addicted to autophagy for continued growth and have motivated the development of two clinical trials at the Dana-Farber Harvard Cancer Center for the treatment of pancreatic cancer patients. Kimmelman is also an attending radiation oncologist at the Dana-Farber Cancer Institute and Brigham and Womens Hospital, specializing in gastrointestinal malignancies.

David A. Tuveson, MD, PhD

Cold Spring Harbor Laboratory
e-mail | website | publications

David Tuveson is professor and deputy director of the Cancer Center at Cold Spring Harbor Laboratory. Tuveson holds MD and PhD degrees from Johns Hopkins. Tuveson was a medical resident at Brigham and Women's Hospital and a medical oncology fellow at Dana-Farber/Partners Cancer Care. During his postdoctoral years, Tuveson co-developed KIT inhibitors for gastrointestinal stromal tumors with George Demetri. Simultaneously, he generated several widely-used mouse cancer models with Tyler Jacks. As an independent investigator, his lab generated the first mouse models of ductal pancreatic cancer at the University of Pennsylvania. Subsequently, Tuveson was recruited to the University of Cambridge to develop preclinical and clinical therapeutic strategies for pancreatic cancer. His lab identified a variety of parameters that limit therapeutic efficacy in pancreatic cancer, including poor drug delivery and survival factors in the microenvironment. These findings are currently undergoing clinical evaluation. Tuveson now directs the Cancer Therapeutics Initiative at Cold Spring Harbor Laboratory and serves as director of research for the Lustgarten Foundation. He continues to practice medical oncology with an adjunct appointment at Memorial Sloan-Kettering Cancer Center. His awards include the Rita Allen Scholarship.


Megan Stephan

Megan Stephan studied transporters and ion channels at Yale University for nearly two decades before giving up the pipettor for the pen. She specializes in covering research at the interface between biology, chemistry, and physics. Her work has appeared in The Scientist and Yale Medicine. Stephan holds a PhD in biology from Boston University.

Sponsors

Academy Friends

The Lustgarten Foundation

Transnetyx

Mission Partner support for the Frontiers of Science program provided by: Pfizer