Clinical Translational - Lustgarten Foundation: Pancreatic Cancer Research

Clinical Translational

Driving Clinical Collaborations to Improve Patient Outcomes

Andrea Califano, Ph.D.

Clyde and Helen Wu Professor of Chemical and Systems Biology
Columbia University

Kenneth Olive, Ph.D.

Assistant Professor of Medicine
Assistant Professor of Pathology & Cell Biology

Columbia University
Funding: $2.2 million over 3 years (2018-2020)
Project: Clinical translation of regulatory network-based precision medicine for pancreatic cancer

“OncoTreat” is a computational framework that pairs patients with optimal regimens in a completely new way. Rather than using DNA mutations, the approach reads the dynamic messages found in the RNA of tumor cells and interprets these to identify critical vulnerabilities of the tumor that may be attacked with one or more drugs. Building upon the success OncoTreat has had in other cancers, this grant supports a clinical trial of the OncoTreat framework in pancreatic cancer patients as well as associated preclinical studies. The team is analyzing the tumor RNA of each patient and uses supercomputer methodologies to predict which existing drugs will best target that tumor. Samples of each patient’s tumor are transplanted into mice as a surrogate model in which to test the top predicted therapies that are readily available. The top validated agent will then be used to determine the optimal treatment for each patient in the second line setting, with the goals of assessing safety/feasibility and identifying early indications of efficacy of the RNA-based precision medicine approach.  Learn more about personalized medicine.

About Dr. Califano:
Dr. Califano is currently the founding director and chair of the Columbia Department of Systems Biology, which includes the Sulzberger Columbia Genome Center and the Center for Computational Biology and Bioinformatics (C2B2). He also serves as Associate Director for Bioinformatics in the Herbert Irving Comprehensive Cancer Center. Dr. Califano serves on numerous editorial and scientific advisory boards, including St. Jude Children’s Hospital, the Sanford-Burnham Institute, MD Anderson Genomic Medicine department, and the National Cancer Institute.

About Dr. Olive:
Dr. Olive’s lab is dedicated to finding a cure for pancreatic cancer. They perform preclinical therapeutics trials using advanced genetically engineered mouse models of pancreatic cancer to treat mice with pancreatic cancer in exactly the manner that human patients are treated. Tumor volumes are tracked and quantified using advanced small animal imaging technologies such as high resolution ultrasound and optical imaging, and mice are enrolled into randomized therapeutics trials. Ultimately, successful therapies will be translated into the clinical settling through collaborations with the Pancreas Center of Columbia University.

A discussion with Dr. Olive:

LF: What is the impact of your work?
KO: Although some modest progress has been made in recent years, treatment for pancreatic cancer is still essentially based on just a few chemotherapy regimens. Our methodology has the potential to offer personalized treatment options for the large majority of pancreatic cancer patients using agents that are already in the clinic. If validated, the approach has the potential to immediately offer more effective treatment options on a patient-by-patient basis.

LF: Why is this funding important for your research?
KO: The NIH has been extremely supportive of our work in the basic sciences and is supportive of clinical work performed with standard approaches (i.e. one-target-one-drug). However, our methodology breaks with the one-target-one-drug mold and as a result, it would be considered too high-risk to be funded via standard NIH support mechanisms. The Lustgarten Foundation is among the very few organizations that are poised to fund high-risk, breakthrough work that could dramatically impact patient lives in a short period of time.

LF: What is your message to patients?
KO: Now, more than ever before, we have an unparalleled suite of tools, approaches and technologies available that together enable us to look deeply into their tumors and the critical vulnerabilities that can be tackled with existing drugs. Our understanding has exploded exponentially over the past few years. We truly believe we are in a time when major breakthroughs for patients suffering from this terrible disease are going to be realized.

Brian Wolpin, M.D., MPH

Dana-Farber Cancer Institute
Funding: $1.7 million over 3 years (2017-2019)
Project: Real-time organoid drug profiling to inform personalized therapy for patients with metastatic pancreatic cancer

Dr. Wolpin and his team take a multi-pronged approach to implementing personalized medicine
for patients with pancreatic cancer. One approach focuses on genetic sequencing of both the tumor DNA and the inherited DNA from each patient. The sequencing findings are used to identify new treatment programs for patients, which may include off-label use of medications that treat other cancers or enrollment on clinical trials. This can also lead to identification of inherited causes of pancreatic cancer, so genetic counseling and testing of family members can also be an important aspect of care for some patients. A second personalized medicine approach used by Dr. Wolpin and his team involves growing three-dimensional organoid cultures in the laboratory from fresh tissue biopsies and testing dozens of drugs to identify sensitivities specific to that patient’s tumor. Dr. Wolpin is collaborating with Drs. Andrew Aguirre and William Hahn at Dana-Farber to determine whether drugs that are effective in treating a patient’s organoid in the laboratory also work well in treating the patient in clinic. This approach provides another opportunity to identify personalized therapy recommendations for patients. Dr. Wolpin and his team also continue to evaluate additional approaches to personalized treatment, using additional tests on patient blood samples and tumors. In aggregate, the primary goal of this work is to treat patients as individuals based on the characteristics of their cancer, rather than using a one size fits all approach.  Dr. Wolpin has recently published papers on his work.  learn more about personalized medicine.

About Dr. Wolpin:
Dr. Wolpin is the director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute. He is also an associate professor of medicine at Harvard Medical School, and the Robert T. and Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber.

Dr. Wolpin’s research group conducts studies evaluating blood-based circulating markers, germline alterations, and somatic alterations in hundreds to thousands of subjects, in an effort to understand the factors that promote initiation and progression of pancreatic cancer. The near-term aim of their work is to translate cutting-edge laboratory science into approaches for early detection of pancreatic cancer and to develop new treatments for patients.

In his clinical practice, Dr. Wolpin cares for patients with gastrointestinal cancers, with a focus on pancreatic cancer. He holds several leadership positions related to clinical expertise, including membership on the NCI Pancreas Cancer Task Force, Alliance/CALGB Gastrointestinal Cancer Committee, and NCCN Guidelines Committee for Pancreatic Adenocarcinoma.

A discussion with Dr. Wolpin:

LF: What is the impact of your work?
BW: The goal of our work is to improve the detection and treatment of pancreatic cancer. We have multiple ongoing studies testing new ways to detect pancreatic cancer earlier, when it has a higher likelihood of being cured. And we work to identify personalized treatment approaches for patients with pancreatic cancer once it is diagnosed. With this work, we hope to increase from pancreatic cancer and improve quality and length of life for patients with the disease.

LF: Why is this funding important for your research?
BW: Funding from the Lustgarten Foundation has been and continues to be absolutely critical to the advancement of our research. This support provides needed seed funds to start new projects and test new hypotheses. It also allows us to take promising ideas and expand them out to the larger studies necessary to more definitively evaluate our findings. Furthermore, these funds help support the work of post-doctoral fellows and junior faculty in the group, cultivating the next generation of scientists who will work to cure pancreatic cancer.

LF: What is your message to patients?
BW: We have a tremendous amount of hope for patients with pancreatic cancer. The understanding of this disease is expanding rapidly. Each day we learn more about its vulnerabilities and test new ways to find it early and treat it better. In addition, more patients are being cured and living longer today than in years past, and the pace of these improvements is accelerating. A large and dedicated community of scientists and clinicians are working to quicken the pace of discovery and success. We all look forward to the day soon when pancreatic cancer becomes a highly curable and manageable disease.

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