Innovations in cancer treatments start with discoveries in the laboratory – which is where Fox Chase Cancer Center continues to make powerful inroads to advance care for cancer patients in the local community and throughout the world.
As Co-Directors (along with Dr. Sanjay Reddy) of the Marvin and Concetta Greenberg Pancreatic Cancer Institute at Fox Chase, Drs. Igor Astsaturov and Edna (Eti) Cukierman rise up every day to take on the challenge of pancreatic cancer, where patients are facing the lowest survival rates of all cancers. Both are firm believers that victory over this deadly disease will be driven by lab-based discoveries in early detection and treatment targets. And this is where basic science comes into play.
The two scientists are not alone in the fight against pancreatic cancer, thanks to the collaborative network of experts within the institutional Cancer Signaling and Microenvironment Program – which involves the study of cancer cell signaling, their cancer cell-intrinsic adaptation, and how they are affected by cell-cell communication with other non-cancerous cells of the tumor microenvironment (TME). The focus on the pancreatic cancer microenvironment by the scientists at Fox Chase has uncovered greater insights into cancer cells and their TME through this holistic lens, gaining a richer understanding of cancer biology while spurring new translational treatment strategies and potential new drugs.
For these world-class researchers, their work is meaningful and challenging not just because pancreatic cancer is so dangerous, but even more because its biology is unique among all other cancers. Pancreatic cancer is notable by its large “neighborhood” (i.e., the TME) of non-cancerous cells that make up the majority of the tumor mass. These cells may lose their natural ability to suppress cancer and may even end up contributing to tumor development and progression. This is because the TME serves to directly facilitate nutritional support for the cancer cells, while the immune system becomes less equipped to fight them off.
“Together with the entire Greenberg Institute, we are testing whether we can harness the anti-tumor natural functions of our body – including in the organ and the immune system – and find a holistic way to treat the entire patient using the models we have developed in the lab,” Dr. Cukierman says.
“When you put together a multidisciplinary group of physicians, population scientists and basic scientists and they’re all looking at the psychology and stress of the patient, whether the patient may be more active or has certain dietary cultural preferences – that is truly where individualized medicine comes from. And that is why what we’re doing is so profoundly different from everybody else.”
In an ongoing productive collaboration, the Astsaturov and Cukierman laboratories are currently conducting in-depth analyses of the role of cancer-associated fibroblasts (CAFs) in pancreatic cancer – with a specific focus on how CAFs provide the tumor cells with essential lipids such as cholesterol and other membrane lipid particles. Ultimately, their project aims to uncover metabolic vulnerabilities in the cholesterol pathway to help develop new strategies for disrupting those interactions between CAFs and cancer cells.
“This research is about finding an intelligent mechanism to understand how the cancer cells interact with the microenvironment, or how they derive the nutrients and activating signals and how we can block those, so we can keep cancer cells from becoming more aggressive,” Dr. Astsaturov says. “Once we know the target, we come up with the drug, we develop a concept, we publish it, and then we subsequently go to clinical trials as we strive to directly help patients. That is the long-term goal of all the research we do.”
Drs. Astsaturov and Cukierman have joined forces on multiple research projects for pancreatic cancer, often with collaborators from other institutions in the United States. One notable study involved the identification of a new biomarker and potential novel treatment target that could help starve cancer cells and empower the immune system to attack the tumor. The target, a brain synaptic protein called Netrin G1 (NetG1), was found by the Cukierman lab to be ectopically expressed in the tumor-promoting fibroblastic cells of the pancreas, supporting cancer cell survival in low-nutrient conditions while inhibiting the immune system from fighting the cancer.
While ongoing efforts to target the above-mentioned pathways are under way, the two collaborators also have made inroads in the field of pancreatic cancer metabolism. Their efforts have recently identified a mechanism by which pancreatic cancer cells acquire lipids by coercing the fibroblastic cells to feed them their membranes, contributing to sustained tumor growth. This discovery could help overcome serious issues with treatment resistance and metastatic spread. The team is now designing a clinical trial with an idea to block this feeding process with existing, FDA-approved drugs.
“The study of cancer biology is the springboard to propelling smart and effective treatments for our patients,” Dr. Astsaturov says. “In the field of pancreatic cancer, I am convinced that the treatment choices for each individual patient will soon be defined by the molecular makeup of their cancer cells. This knowledge can help us match the treatment strategies with the biology of the individual patient’s tumors.”
As part of this effort, Dr. Astsaturov and the Fox Chase clinical team are preparing to launch a clinical trial of a new chemotherapy drug called LP-184 for pancreatic cancers marked with deleterious mutations in DNA repair.
Pancreatic cancer is on track to become the second-leading cause of cancer-related death in the United States, with about 80 percent of patients dying within the first year of diagnosis. Yet, the disease remains alarmingly under-studied. That’s why the role of the Marvin and Concetta Greenberg Pancreatic Cancer Institute – and its leaders – is so significant.
The Institute, which opened in September 2017, represents a groundbreaking investment in the collaboration of scientists, researchers and physicians at Fox Chase. This multidisciplinary team works together to disrupt the pancreatic cancer metabolism that promotes immunosuppression. In addition to a world-class basic science program, the Institute features an active translational research program and an active clinical research team that has first focused on the concept of neoadjuvant (presurgical) therapy for pancreatic cancer patients, using surgical samples and other tissues for testing their lab-generated hypotheses.
Dr. Astsaturov says Fox Chase has created the ideal environment for researchers to succeed. “I am deeply convinced that the best way to help our patients is to push the boundaries by doing clinical and basic research,” he says. “Fox Chase offers an intellectual cross-pollination across disciplines and the opportunity to have experts on multiple areas of science and clinical care of cancer. That team-centric environment has tremendous benefits for those of us who work as both a physician and a scientist so we can collaborate on driving innovations in both fields.”
Fox Chase is designated as a National Pancreas Foundation Center by the National Pancreas Foundation, a nonprofit organization that provides support for patients with pancreatic cancer and other related diseases. As the only institution in the Philadelphia region to earn this distinction, Fox Chase is designated as both a Clinical and Academic Center of Excellence for Pancreatic Cancer.
“That collaboration between our researchers and physicians is integral to the success of our efforts, and our dedication to this at the Institute will lead to even more clinical trial options for patients,” Dr. Astsaturov says.
With a long and storied history of breakthrough research, Fox Chase continues to lead the field with seminal scientific discoveries that have key translational implications. The insights gleaned from these laboratory studies can be directly applied to patient care while safely evaluating new approaches to preventing and treating cancer through clinical trials, which may eventually drive standard protocols with far-reaching implications.
That’s the benefit of Fox Chase’s elite standing as an NCI-designated Cancer Center: Our research is led by extraordinarily talented scientists who work in an ideal environment for fundamentally important discoveries. With additional support from our partnership with Temple University Health System’s oncology research, treatment and prevention programs, Fox Chase research makes a world of difference in Northeast Philadelphia and all other communities that we serve.
“We are tailoring everything we do to benefit the specific population of our patients in the Philadelphia area and meet their unique clinical needs,” Dr. Cukierman says. “Fox Chase is made up of a tremendous group of world-renowned clinicians in that they go out to meet and listen to our communities so they can convey those messages back to the Cancer Center members. There are no silos here – we’re all in it together for the good of everybody else. And I am proud to say I am challenged every day.”
As one of the four original cancer centers to receive comprehensive designation from the National Cancer Institute, Fox Chase Cancer Center has been at the forefront of cancer research for more than 100 years. With a singular focus on cancer, we combine discovery science with state-of-the-art clinical care and population health.
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