The Lustgarten Foundation Dedicated Pancreatic Cancer Research Laboratories
Building on the success of our first dedicated pancreatic cancer research lab at Cold Spring Harbor Laboratory, we have opened three additional labs at Dana-Farber Cancer Institute, Massachusetts Institute of Technology, and Johns Hopkins. Together, these labs position the Foundation as the only non-profit in the country to have four labs dedicated to pancreatic cancer research, which means more resources, time and talent are being put toward this disease. United in the shared goal of improving patient outcomes, these labs will increase collaboration between world-renowned pancreatic cancer researchers and explore new, promising avenues for understanding and treating pancreatic cancer.
The Lustgarten Foundation Pancreatic Cancer Research Laboratory
In 2012, the Lustgarten Foundation established a dedicated world-class laboratory at Cold Spring Harbor Laboratory to focus exclusively on pancreatic cancer research. In the United States, there are only a handful of labs that are dedicated to pancreatic cancer research, so partnering with a major laboratory is incredibly important for the advancement of pancreatic cancer research.
The Cold Spring Harbor Laboratory (CSHL), located in scenic Cold Spring Harbor, New York, is a leading biomedical research and education lab, that houses programs in cancer, neuroscience, plant biology and quantitative biology. The CSHL Cancer Center is an NCI-designated cancer center dedicated to the advancement of cancer research. Since the lab was established in 1890, there have been eight Nobel Prize winners who have conducted research at the lab, and the lab hosts more than 12,000 scientists from around the world annually.
Lab Leadership: David Tuveson, M.D., Ph.D.
Heading up the Lustgarten lab is internationally renowned physician-scientist Dr. Tuveson, who holds a dual appointment as the Director of the Cold Spring Harbor Laboratory Cancer Center and the
Roy J. Zuckerberg Professor of Cancer Research at Cold Spring Harbor Laboratory and Chief Scientist at the Lustgarten Foundation.
Dr. Tuveson has impressive academic credentials and a long history of conducting groundbreaking research in the field of pancreatic cancer. As a physician-scientist, Dr. Tuveson merges his laboratory research with his clinical research and can bring new options to patients more rapidly.
During his tenure at the University of Pennsylvania, Dr. Tuveson generated the first genetically engineered mouse for pancreatic cancer, a model which is now used throughout the scientific community to test new therapies for pancreatic cancer.
While a professor at the University of Cambridge, Dr. Tuveson discovered that pancreatic cancer tumors develop a protective membrane, or stroma, which prevents chemotherapy from reaching cancer cells. He concluded that the dismal effectiveness of standard chemotherapy in treating pancreatic cancer could be due to the inability of the drug to reach its target. Moving forward, Dr. Tuveson and other scientists are concentrating on combining drugs designed to penetrate the stroma to treat patients more effectively.
His recent and most promising work has been on organoids, three-dimensional cell culture systems which reproduce a patient’s tumor in a dish in order to test is repeatedly, with the aim of identifying new potential treatments. Dr. Tuveson was the first scientist to use organoids for pancreatic cancer and has been a pioneer in developing organoids to determine which chemotherapy drug a patient’s tumor would respond best to. This type of research is known as personalized medicine and allows doctors to treat each patient with a customized treatment plan to maximize efficacy and improve quality of life.
Research at the Lab
The Lustgarten laboratory works on many aspects of pancreatic cancer including new therapeutic and diagnostic platforms. The lab is broken down into four main research areas: organoids, biomarkers, biology, and therapeutics.
Organoids for Pancreatic Cancer
The Lustgarten lab has been able to utilize organoid technology to bring a personalized medicine approach to the treatment of pancreatic cancer. By treating the organoid in the laboratory with many compounds and combinations of compounds to determine which are most effective in killing the cancer cells, patients in a clinical setting will be more likely to receive the drug that their tumor will respond to—the first time around. This is especially important for pancreatic cancer patients because they typically do not have time to try several different treatments to fight their disease, which is often not diagnosed until it is at an advanced stage. Learn more about organoids.
A biomarker is a biological molecule found in blood, fluid, or tissue that can be a sign of a condition or disease, and it can also be helpful in determining if a patient is responding to a certain treatment. The goal of the biomarker work is to find ways to detect pancreatic cancer sooner and have more patients be eligible to undergo surgery—which offers patients the best chance for long term survival. Researchers in this group focus on early detection methods and also utilize organoids to determine which chemotherapy drugs a patient would benefit from the most. While utilizing organoids as a treatment mechanism is still in the early stages of development, it has shown promising results and researchers hope that they will soon be able to grow and test the organoids faster so that they can offer patients the best chemotherapy drug for their tumor as a first-line treatment.
Researchers are also studying CA 19-9, a protein found in blood that is most commonly caused by pancreatic cancer. This biomarker can be a way to monitor pancreatic cancer patients after surgery and to track a potential relapse. Researchers are working to develop CA 19-9 as a tool to produce a more reliable biomarker that could lead to earlier detection of a pancreatic tumor.
There are many components that make up a pancreatic tumor and can complicate diagnosis and treatment. Researchers are focusing on the stroma and trying to understand the role it plays in pancreatic cancer. The stroma is a hard tissue that surrounds the pancreas and often impedes the ability of chemotherapy drugs to reach the targeted cancer cells. Dr. Tuveson likens the stroma in pancreatic cancer to that of an oatmeal-raisin cookie, where the raisins represent tumor cells and the oatmeal is the stroma. If you wanted to pick the raisins out, you would have to break up the oatmeal. That’s what researchers are trying to do by examining how certain cells help the cancer thrive, while other cells restrain the cancer cells in the stroma.
Researchers are also studying fibroblasts, which are long cells that are found in the protective layer of the stroma. In a recent paper, Cold Spring Harbor Laboratory researchers explained their discovery that there are two distinct entities of fibroblasts and that they each have different functions. By studying the signals that make the different fibroblasts what they are, researchers hope that they can get a better understanding of the cells that support cancer cells.
The therapeutics work focuses on testing new therapies that can target cancer cells, looking specifically at therapies that have not made it into the clinic to be tested yet.
One way new therapies can be studied in the lab is through utilizing organoids and testing treatment options to see which existing or investigational therapy has the best response rate. Researchers hope to learn why some patients are very sensitive to certain chemotherapy drugs while others are resistant. Ongoing research is being conducted to try to identify gene signals that can be extracted from a biopsy that will tell which patients will respond to standard chemotherapy.
About Dana-Farber Cancer Institute
Since its founding in 1947, Dana-Farber Cancer Institute in Boston, Massachusetts has been committed to providing adults and children with cancer with the best treatment available today while developing tomorrow’s cures through cutting-edge research.
Lab Leadership: Brian Wolpin, M.D., MPH
Dr. Wolpin is a medical oncologist who sees patients and serves as director of the Gastrointestinal Cancer Center, Director of the Hale Family Center for Pancreatic Cancer Research, and the Robert T. & Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber Cancer Institute. His research program is dedicated to the investigation of pancreatic ductal adenocarcinoma (PDAC) biology and treatment.
Dr. Wolpin has built multiple human subject resources to facilitate investigation of blood-based markers, germline alterations, and somatic alterations in hundreds to thousands of subjects. He leads a highly productive collaboration of Harvard prospective cohort studies that leverages prediagnostic blood specimens to identify novel circulating markers for PDAC. His group has developed extensive expertise in analyzing markers of altered metabolism.
Dr. Wolpin serves as co-principal investigator for the Pancreatic Cancer Cohort Consortium, a multi-institutional NCI-based consortium studying inherited genetics of sporadic PDAC. Together, they have performed the first large-scale genome-wide interrogations of genetic variation and PDAC risk. Additionally, he is chair of the NCI Pancreatic Cancer Detection Consortium Steering Committee and leads a PDAC biospecimen bank at Dana-Farber that collects patient data, blood specimens, and tumor samples for studies of new early detection and predictive biomarkers.
Dr. Wolpin is also the principal investigator (PI) of a project to establish a translational science pipeline focused on serial biospecimen collection to understand mechanisms of therapeutic response and resistance in pancreatic cancer. Collectively, his group has extensive experience in generating and analyzing large, complex, multi-dimensional datasets related to PDAC development and progression.
Research at the Lustgarten Laboratory at Dana-Farber
Dr. Wolpin’s laboratory focuses on diagnosis, risk factors, survival determinants, and clinical trials for pancreatic ductal adenocarcinoma (PDAC). Dr. Wolpin’s research is able to translate to his patients in real time. The research conducted in the Lustgarten Laboratory at Dana-Farber will focus on three main objectives:
- Study the genetic composition and functionally characterize the driver pathways of pancreatic tumors, which will lead to personalized treatment options for patients;
- Expand clinical trials for patients with metastatic pancreatic cancer, in which treatments are selected using organoids, or miniature 3-D tissue samples taken from a patient’s tumor. Organoids allow multiple drugs to be tested in real time to identify the best course of treatment for the patient; and
- Identify new blood-based and imaging markers of asymptomatic pancreatic cancer and new models for pancreatic cancer risk prediction to facilitate earlier cancer detection.
About the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, based in Baltimore, Maryland, is one of 49 centers designated by the National Cancer Institute as a comprehensive center. Learn more at www.hopkinscancer.org.
Lab Leadership: Bert Vogelstein, M.D.
Dr. Vogelstein is Director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School and Kimmel Cancer Center.
Dr. Vogelstein has published more than 500 scientific papers. Dr. Vogelstein’s research papers have been cited nearly 300,000 times, more often than those of any other scientist, in any discipline, in recorded history. If books in addition to research papers are included, Dr. Vogelstein is ranked as the 8th most cited scholar of all time, with Sigmund Freud ranking first.
Beginning in 2004, Dr. Vogelstein and colleagues began to perform large-scale experiments to identify mutations throughout the genome. They were the first to perform “exomic sequencing,” where they determined the sequence of every protein-encoding gene in the human genome. The first analyzed tumors included those of the colon and breast. The Foundation then recruited
Dr. Vogelstein to sequence the genetic makeup of pancreatic cancer, which was a significant turning point in pancreatic cancer research.
Following up from this landmark research, Dr. Vogelstein is focusing his research efforts on developing earlier detection tests.
Research at the Lustgarten Laboratory at Johns Hopkins
Under Dr. Vogelstein’s leadership, the Lustgarten Laboratory at Johns Hopkins will leverage its expertise in early detection to intercept pancreatic cancer at an earlier stage when patients may be surgical candidates and will develop novel therapeutic approaches to treat pancreatic cancer based on genetic alterations.
Dr. Vogelstein and his team developed CancerSEEK, a blood test for the detection of pancreatic cancer (and other cancers), that has been given “Fast-Track” status for pancreatic (and ovarian) cancers by the Food and Drug Administration (FDA), which will accelerate the approval process and may lead to a method to detect pancreatic cancer earlier for patients.
In parallel, Dr. Vogelstein’s team developed a Comprehensive Cyst (CompCyst) test, which combines clinical, radiological, genetic and protein marker information to distinguish if pancreatic cysts, which can be common amongst the general population, can develop into pancreatic cancer or remain as benign cysts.
Based on preliminary findings, the main objectives of the early detection studies for the Lustgarten Laboratory at Johns Hopkins will be:
* Increase the CancerSEEK sensitivity (the ability to correctly identify those with the disease) for the detection of pancreatic cancer by evaluating new protein biomarkers and improving the specificity (the ability to correctly identify those without the disease) through the evaluation of circulating tumor DNA (ctDNA) detection.
* Further develop the CompCyst test into a clinically approved test for many people harboring pancreatic cysts.
The second area of investigation for Dr. Vogelstein’s dedicated laboratory will be the development of new therapeutic approaches that target the genetic alterations in pancreatic cancer, called MANAs (Mutation-Associated NeoAntigens). A newly developed method by Dr. Vogelstein’s team, called MANAFESTA, can help monitor the effectiveness of immunotherapy in patients being treated for cancer by examining a patient’s MANA-specific T-cells.
To develop new treatment approaches for pancreatic cancer that target the genetic alterations, the Lustgarten Laboratory at Johns Hopkins will work to:
* Develop MANAs antibodies for KRAS and TP53, the most common genetic mutations found in pancreatic cancer patients.
* Identify T-cell receptors that can bind to mutant KRAS and TP53 peptides, leading to a new targeted therapy.
About Koch Institute for Integrative Cancer Research at MIT
The Koch Institute for Integrative Cancer Research, a National Cancer Institute (NCI)-designated Cancer Center, is a state-of-the-art cancer research facility as well as the hub of cancer research on the MIT campus. The Koch Institute brings together biologists and chemists along with biological, chemical, mechanical, and materials science engineers, computer scientists, clinicians and others, to bring fresh perspectives and an interdisciplinary approach to advancing the fight against cancer. This multi-faceted group of investigators is at the core of the Koch Institute’s mission to develop new insights into cancer, as well as new tools and technologies to better treat, diagnose and prevent the disease.
Lab Leadership: Tyler Jacks, Ph.D.
Dr. Jacks is a Professor of Biology at the Massachusetts Institute of Technology (MIT), a Howard Hughes Medical Institute investigator, and director of the David H. Koch Institute for Integrative Cancer Research, which brings together biologists and engineers to improve detection, diagnosis, and treatment of cancer. Professor Jacks received his bachelor’s degree in biology from Harvard College, and his doctorate from the University of California, San Francisco, where he trained with Nobel Laureate Harold Varmus. He was a postdoctoral fellow with Robert Weinberg at the Whitehead Institute before he joined the MIT faculty in 1992.
In recognition of his contributions to the study of cancer genetics, Dr. Jacks received the American Association for Cancer Research (AACR) Outstanding Achievement Award, the Amgen Award from the American Society of Biochemistry and Molecular Biology, the Paul Marks Prize for Cancer Research, and the Sergio Lombroso Award in Cancer Research. He also served as Chair of the National Cancer Advisory Board at the National Cancer Institute, was a member of the Board of Directors of the AACR and was elected President of the AACR in 2009. Dr. Jacks was also elected to the National Academy of Sciences, the Institute of Medicine of the National Academies, the American Academy of Arts and Sciences and the inaugural class of Fellows of the AACR Academy. In 2015, he was the recipient of the Killian Award, the highest honor the MIT faculty can bestow upon one of its members, and he is currently serving as co-chair of the Blue Ribbon Panel for Vice President Joe Biden’s Cancer Moonshot Initiative.
Research at the Lustgarten Laboratory at MIT
Dr. Jacks’ laboratory is studying the genetic events contributing to the development of cancer. The focus of its research has been a series of mouse strains engineered to carry mutations in genes known to be involved in human cancer. The Lustgarten Laboratory at MIT will leverage its unparalleled expertise in cancer biology and engineering to advance pancreatic cancer research. The main objectives of the Lustgarten Laboratory at MIT will be to:
- Evaluate the role the immune system plays in the development of pancreatic tumors and progression of the disease to lead to better therapeutic options;
- Explore pancreatic cancer progression using single cell profiling technologies, which will provide new insights into the mechanisms of disease development as well as identify new targets for intervention;
- Reduce the time required to produce an organoid; and,
- Use organoids and mouse models with specific mutations to examine genes that may be responsible for tumor development and explore DNA manipulation through screenings to examine disease progression.