Normal cells become cancerous through a set of steps that result in the continuous activity of signaling pathways that stimulate their multiplication and dissemination to other sites in the organism. A major objective of many research efforts is to identify molecules that target dysregulated pathways in the hope of restoring normalcy to the proliferation of cancer cells. One of the pathways that have emerged as of central importance in driving the unbridled multiplication of many types of cancer, including pancreatic cancer is the mTOR pathway. Inhibitors of this pathway have been identified but their therapeutic efficiency is far from optimal. The reason(s) of this limited activity is the area explored in this new paper, published in PLoS ONE, by Dr. Rozengurt, the Hirshberg Foundation Chair in Translational Pancreatic Cancer Research. The team, working with pancreatic cancer cells, have used drugs targeting the mTOR pathway and examined the activity of this pathway and other pathways known to be frequently dysregulated in pancreatic cancer. Interestingly, the block in mTOR by novel direct inhibitors not only suppressed the activity of the intended target but surprisingly, also induced robust activation of the MEK/ERK pathway, a central multiplication-inducing pathway linked to the oncogene Ras, the most commonly activated oncogene in pancreatic cancer. The first important conclusion of this manuscript is that the unexpected over-activation of a pathway like the MEK/ERK can counterbalance the inhibitory effects of the drug on its target, mTOR, thus limiting the clinical activity of these inhibitors.

Another molecule that interferes with the mTOR pathway is metformin, the most common drug used in the control of type II diabetes (T2D). There is an epidemic of T2D in the USA (> 20 million people) which is associated with obesity which in turn has increased to an alarming level. A series of recent reports, including a set of papers of papers from the Rozengurt team, indicated that metformin also inhibits the multiplication of pancreatic cancer cells, at least in part via blockade of mTOR. The new paper in PLoS ONE discovered a fundamental difference in the cellular action of metformin as compared with that of direct mTOR inhibitors in pancreatic cancer cells: metformin did not produce over-activation of the ERK pathway but instead suppressed it. If the new findings with cells in culture can be extended to cancer cells in tumors, the results could explain important aspects of the anticancer activity of different drugs that target mTOR and excitingly, suggest rational drug combinations for combating pancreatic cancer in the future.

Link to Full Article

Final

Media Contact:
Donald Wilson
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THE HIRSHBERG FOUNDATION FOR PANCREATIC CANCER RESEARCH ANNOUNCES THE 2012-2013 SEED GRANT AWARD RECIPIENTS

LOS ANGELES, Calif., – (November 1, 2012) – Known for supporting budding young scientists and being a strong and dominant leader throughout the pancreatic cancer research community, the Hirshberg Foundation for Pancreatic Cancer Research announces the 2012-2013 Seed Grant Award recipients. The Seed Grant Award provides start-up funding for basic scientists and clinicians to test innovative ideas for improving diagnostics as well as develop new treatment modalities with a current approach to the understanding of pancreatic cancer.

The Hirshberg Foundation launched the Seed Grant program in 2000 to scientific investigators from major cancer centers in the United States. The success of the grant recipients in publishing and attracting National Institutes of Health (NIH) funding has been instrumental in advancing scientific research. The Seed Grant program continues to promote the expansion of pancreatic cancer programs nationally and internationally in addition to collaborations within the scientific community.

“We are changing global research efforts through the Hirshberg Foundation’s Seed Grant Program,” said Agi Hirshberg, president and founder of the Hirshberg Foundation. “Our joint efforts on all fronts could change the outcome of a pancreatic cancer diagnosis, but private funding still remains the hope for a cure and this means our call to action is stronger than ever.”

Out of 44 submissions, seven were honored with the 2012-2013 Seed Grant Award:
Alexandros Tzatsos, M.D., Ph.D.
Instructor in Medicine at Massachusetts General Hospital Cancer Center
•    Research Thesis: “Validation of the histone demethylase KDM2B as a new therapeutic target in pancreatic cancer”
 
Anne Coscarelli, Ph.D.
Clinical Professor of Psychology at the University of California Los Angeles
•    Research Thesis: “Providing optimal psychosocial support to patients and families through the journey of pancreatic cancer”
 
Ido Wolf, M.D.
Senior Lecturer, Tel Aviv University at Tel Aviv Sourasky Medical Center’s Oncology Department
•    Research Thesis: “The hormone klotho: a novel regulator of the ERK1/2 cascade in pancreatic adenocarcinoma”
 
Isidore Rigoutsos, Ph.D.
Director of Computational Medicine Center at Thomas Jefferson University
•    Research Thesis: “New Vistas for Gene Regulation in Pancreatic Cancer”
 
Mouad Edderkaoui, Ph.D.
Research Scientist at Brentwood Biomedical Research Institute
•    Research Thesis: “Targeting EMT pathway as a promising strategy for pancreatic cancer treatment”
 
Parkash Gill, M.D.
Professor of Medicine and Pathology at University of Southern California (Hematology Department)
•    Research Thesis: “Role of EphB4 in Kras Mutant PDAC”
 
Qing-Yi Lu, M.D., Ph.D.
Associate Professor & Core Director at the University of California Los Angeles
•    Research Thesis: “The Phytonutrient Core of the UCLA Center for Excellence in Pancreatic Diseases”
 
With the assistance of the Seed Grant Award, a previous recipient recently made an exciting advancement in pancreatic cancer research. Dr. Ashok Saluja, Ph.D., Professor and Vice Chair of Research for the Department of Surgery at the University of Minnesota Masonic Cancer Center was a Hirshberg Foundation Seed Grant Award recipient in 2007. He discovered the revelation of Minnelide as a promising treatment for pancreatic cancer. The first human trials with Minnelide will begin in 2013.  Minnelide is a novel new drug for pancreatic cancer that is based on triptolide, a compound extracted from a Chinese plant and serves as an effective protective protein inhibitor (HSP70) that kills pancreatic tumor cells. The early support Dr. Saluja received from the Hirshberg Foundation served as a major cornerstone for funding obtained from the NIH ($2.6 million) and other sources ($2 million). It is the relentless and passionate goal of the Hirshberg Foundation to focus on early detection and new treatment options. By continuing to sustain the Seed Grant Program and award well-deserved and talented scientists, the Hirshberg Foundation lays the basis for future breakthroughs and eventually finding a cure.

To date, the Hirshberg Foundation funded Seed Grant Award recipients $45 million dollars in NIH grants and raised more than $12 million for pancreatic cancer research. The research mission of the Foundation focuses on the physiology, early diagnosis, treatment and prevention of pancreatic cancer. The Foundation’s programs began at UCLA in 1997 and supports basic science, translational research, as well as a pancreas tissue bank. The programs initially funded by the Foundation at UCLA are now supported by NIH grants.

About the Hirshberg Foundation: Founded in 1997, the Hirshberg Foundation for Pancreatic Cancer Research is a national, non-profit organization dedicated to advancing pancreatic cancer research, and providing information, resources and support to pancreatic cancer patients and their families.

Established by Agi Hirshberg, whose husband Ronald died of pancreatic cancer at the age of 54, the foundation includes the Ronald S. Hirshberg Translational Pancreatic Cancer Research Laboratory; the Ronald S. Hirshberg Chair in Translational Pancreatic Cancer Research; and the Hirshberg Pancreatic Cancer Information Center.

November is Pancreatic Cancer Awareness Month. Pancreatic cancer has the highest mortality rate of all major cancers. In over 40 years, it still remains one of the few cancers for which the survival rate has not improved substantially. Pancreatic cancer is a leading cause of cancer death largely because there are no detection tools to diagnose the disease in its early stages when surgical removal of the tumor is still possible. For more information on the Seed Grant Award Program, the Hirshberg Foundation or pancreatic cancer, visit www.pancreatic.org.

We are pleased to announce that Guido Eibl, M.D., Principal Investigator and Scientific Director of the Ronald S. Hirshberg Translational Pancreatic Cancer Research Laboratory at the UCLA School of Medicine, has been awarded a $10 million Program Project Grant from the National Cancer Institute (NCI). Dr. Eibl came to UCLA in 2000 for a two year research fellowship in the Department of Surgery and, luckily for us, he chose to dedicate his career to the research of the pancreas. In 2009 he was a Hirshberg Seed Grant Recipient* for his work in “western diet induced pancreatic cancer,” a project which propelled his work towards this larger five year study.

The Program Project Grant is titled Targeting Diet-Induced Promotion of Kras-initiated Pancreatic Adenocarcinoma (P01 CA163200-01A1). The purpose of the study is to unravel the mechanisms by which obesity enhances pancreatic cancer development. In addition, strategies to prevent obesity-induced pancreatic cancer will be investigated. Researchers will use a genetically engineered mouse model and a high fat, high calorie diet to mimic human obesity and pancreatic cancer. Preliminary results will be presented at the American Association for Cancer Research (AACR) Special Conference on Pancreatic Cancer in Lake Tahoe, Nevada, in June 2012. The Program Project is a collaborative effort between the Departments of Surgery and Medicine at UCLA and the Department of Veterans Affairs Medical Center in West Los Angeles, CA. The results obtained from the proposed studies will help to clarify the mechanisms, by which obesity promotes pancreatic cancer development and will help to formulate dietary recommendations to potentially lower the risk in high risk patients or prevent the development of pancreatic cancer.

Congratulations to Dr. Eibl and his team at the Ronald S. Hirshberg Translational Lab. We thank all of our supporters for the donations that allow our seed grant program to flourish.

Sincerely,

*The annual Hirshberg Seed Grant Program is a $50,000 one year grant, awarded to investigators to test innovative ideas for improving the outcome for pancreatic cancer. To date, we have funded 44 seed grants.

The foundation’s Lisa Manheim talks about what the we’re doing to fight pancreatic cancer in a recent radio interview on KKLZ.

Download MP3

For Immediate Release

Media Contact:
Donald Wilson
(310) 899-2900
[email protected]

(Los Angeles, California) – On January 31, top clinicians, researchers and physicians from Cancer Centers across the United States presented new developments and progress on finding a cure for pancreatic cancer at the 8th Annual Agi Hirshberg Symposium on Pancreatic Cancer.  The Symposium was hosted by the Hirshberg Foundation for Pancreatic Cancer Research.

Held on the campus of University of California, Los Angeles (UCLA), where the Hirshberg Foundation supports one of the largest pancreatic cancer laboratory programs in the country, this year’s Symposium dedicated to eradicating pancreatic cancer, was the most successful to date. Speakers featured talked about progress in topics ranging from new drug therapies for pancreas cancer to early detection screenings.

Agi Hirshberg, founder of the Hirshberg Foundation for Pancreatic Cancer Research and the Hirshberg Symposium on Pancreatic Cancer said, “I’m very proud of this Symposium as each year we discover advances, bringing us to another step closer to our ultimate goal.”  She added, “Although we’ve made inroads in new drugs, clinical trials and treatments, we still have a long way to go. The cure for pancreatic cancer will not come from one lecture, only through progress.”

The Symposium held dual sessions. The morning’s Medical Session began with six Foundation Seed Grant Program recipients presenting new strategies in management for pancreatic cancer. The afternoon session geared toward Patient and Families consisted of topics including Research and Surgery, Palliative Care and the GI Process for Pancreatic Cancer.  This is the fifth year that the Patient and Family Session was offered and its success continues to grow.

Highlights from the Patient and Family Session featured targeted therapies for pancreas cancer – including research presented by F. Charles Brunicardi, MD, F.A.C.S., UCLA Santa Monica Medical Center on a new clinical trial drug called PDX;  early detection screening developments (presented by C. Melbern Wilcox, MD, University Alabama at Birmingham); and symptom management/patient care during treatment for pancreatic cancer (presented by Thomas Strouse, MD, University of California, Los Angeles). In addition, Diane Simeone, MD, University of Michigan, spoke on targeting pancreatic stem cells and shared exciting news about a clinical trial for metastatic pancreatic cancer patients using a hedgehog inhibitor combined with Gemcitabine.

As an added benefit, the Symposium offered a special extended breakout session where patients and families were given the opportunity to choose which presentation they wanted to participate in.  Topics included emotional support, genetic counseling and legal resources.  Detailed presentations by researchers and physicians can be found on the Hirshberg Foundation’s website at www.pancreatic.org. 

The 8th Annual Agi Hirshberg Symposium for Pancreatic Cancer was sponsored by biopharmaceutical and biotechnology companies, Genentech, Celegene and Amgen.

The Foundation’s dedicated efforts have significantly raised awareness and understanding about pancreatic cancer, a disease that continues to be one of the most fatal and least funded of all cancer types. Their continued funding of basic and translational research is their chance to offer life extension, better treatment options and eventually, a cure. The Hirshberg Foundation staff is able to help when patients and families first receive diagnosis of pancreatic cancer by providing doctor referrals across the United States, second opinion referrals, treatment facility referrals, nutritional information, financial aid information, emotional support information for patients, families and caregivers and someone to talk to that has been through the process from beginning to end.

About the Hirshberg Foundation: Founded in 1997, the Hirshberg Foundation for Pancreatic Cancer Research is a national, non-profit organization dedicated to advancing pancreatic cancer research, and providing information, resources and support to pancreatic cancer patients and their families. It is a tax-exempt organization under Section 501(c)3 of the Internal Revenue Code. The federal tax ID number for the foundation (EIN) is 95-4640311.

Established by Agi Hirshberg, whose husband Ronald died of pancreatic cancer at the age of 54, the foundation includes the Ronald S. Hirshberg Translational Pancreatic Cancer Research Laboratory; the Ronald S. Hirshberg Chair in Translational Pancreatic Cancer Research; and the Hirshberg Pancreatic Cancer Information Center.

To date, the Foundation has:
•    Funded Seed Grant Award Recipients who have received $40 million dollars in NIH grants
•    Raised more than $12 million for pancreatic cancer research
•    Granted over $650,000 in financial aid for patients
•    Provided assistance to thousands of patients and their families
•    Expanded seed grant funding to Loma Linda University, City of Hope, Johns Hopkins Medical Center, Mayo Clinic, Columbia University, University of Minnesota, University of Pittsburgh, Memorial Sloan-Kettering Cancer Center, University of California, San Diego, Harvard Medical School, Duke University Medical Center, Vanderbilt Medical School and University of Arizona Cancer Center.
•    Supported the American Pancreatic Association’s (APA), Japan Pancreas Society, and the European Pancreatic Club’s Annual Meetings
•    Presented the Agi Hirshberg Symposium at UCLA, focusing on research progress and patient and family education 
•    Funded the creation of the Tissue Data Bank at UCLA
•    Awarded international grants to new investigators

Foundation Commitments:
•    Fund medical Symposiums for pancreatic cancer research
•    Fund seed grants for new research projects of merit for pancreatic cancer
•    Consistently update the pancreatic.org site with the latest news and information
•    Host fundraising events to raise awareness and funds for pancreatic cancer
•    Provide financial assistance for patients

By Rachel Champeau October 13, 2011
UCLA RESEARCH ALERT
 
FINDINGS:
A UCLA study has found variations in the types of bacteria found in the saliva of patients with pancreatic cancer and pancreatitis, compared with healthy controls. The findings may offer a new non-invasive biomarker to diagnose and track the development of these diseases. Pancreatic cancer is extremely deadly — only 5 percent of patients survive five years after diagnosis.
 
Previous studies have highlighted periodontal disease, which is related to inflammation of the gums, as playing a possible role in the development of systemic diseases such as heart disease. The current study demonstrates a possible link between this type of inflammation and pancreatic cancer and pancreatitis.
                                  
Researchers found that 31 types of bacterial species were increased in the saliva of patients with pancreatic cancer, compared with healthy controls, and that 25 types of bacteria were reduced. For example, a type of bacteria known as Granulicatella adiacens, which is associated with systemic inflammation, was found to be elevated in pancreatic cancer patients. Also, a bacteria called Streptococcus mitis, which may play a protective role against inflammation, was lower in patients with pancreatic cancer.
 
IMPACT:          
The findings add to growing evidence that saliva may be a credible biomarker source to track and diagnose non-oral diseases. The study also offers new research directions for focusing on inflammation as a contributor to pancreatic diseases.     
 
AUTHORS:       
Dr. James Farrell, M.D., associate clinical professor of digestive diseases and director of the Pancreatic Diseases Program at UCLA, and Dr. David Wong, D.M.D., D.M.Sc., UCLA’s Felix and Mildred Yip Professor of Dentistry, associate dean of research at the UCLA School of Dentistry and director of the UCLA Dental Research Institute, are available for interviews.
 
FUNDING:        
The National Institutes of Health funded the study.
 
JOURNAL:       
The research appears in the Oct. 12 online edition of the peer‑reviewed journal Gut. A copy of the full study is available from UCLA media officers.