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At the New Penn Vet Cancer Center, Collaboration is the Key to Progress

By: Katherine Unger Baillie Published: Aug 31, 2017
By staining for different cell types and cellular activity in the mouse small intestine, researchers are able to determine how changes in diet, genetic alterations, or oncogenic stresses alter the composition and activity of the intestine.

Cancer is the second leading cause of death in humans in the United States, claiming more than half a million lives annually. It’s also a major problem in our companion animals. One in every four dogs and one in five cats will develop cancer in their lifetimes. While cats develop cancer less frequently, their disease tends to be aggressive when it does occur.

Penn Vet’s Oncology team working with a patient.For more than a century, experts at Penn Vet have made breakthroughs in the understanding and treatment of cancer in companion animals. Yet obstacles to advancing veterinary cancer research and care remain.

Notably, the funding base to support research on veterinary cancers is a fraction of that available for cancer research that focuses on humans. And though many cancers that occur in animals share similarities to human cancers, key biological differences often prevent humantherapies from being used effectively in pets.

Now, a new Penn Vet initiative is taking an innovative approach to addressing such challenges—folding in expertise from around the vet school and reaching out to partners across the University. The Penn Vet Cancer Center, which marks its official public launch this fall, will fully integrate research and clinical care, enabling promising discoveries in the lab to rapidly find applications in the clinic.

From the Lab to the Labrador

The formation of the Cancer Center comes at a time when more and more clinicians—both veterinary and human—are moving away from cancer treatments that are based on the organ in which a tumor occurred, and are instead selecting therapies based on the molecular mechanism and genetic profile of a patient’s particular cancer.

Dr. Ellen PuréTo get at this mechanistic understanding, scientists have typically relied on mice. A multitude of reagents have been developed for mice, and they are amenable to the genetic manipulations that allow them to recapitulate certain features of human disease. Yet, treatments that find success in mice often fail to translate to humans.

“Cancer research comes with a lot of failures,” said Dr. Ellen Puré, Professor and Chair of the Department of Biomedical Sciences, who will serve as Director of the Penn Vet Cancer Center. “That’s why cancer drugs cost so much.”

A central aim of the new Cancer Center is to improve the “hit rate” of successful translational therapies by creating a clear path whereby researchers can study cancer and cancer therapies in dogs and cats. In contrast to mice, these animals’ biology more closely mirrors that of humans and, like humans, they can develop cancers spontaneously. Pets also share an environment with humans—in contrast to the closely controlled laboratory conditions in which mice dwell—and thus may share certain environmental risk factors with the people with whom they live.

“The Cancer Center will be a forum for going from the lab to the Labrador, and back to the lab again,” Puré said.

Teaming up to Advance Medicine

The Center will enhance a host of projects involving Penn Vet scientists—many of which consider the tumor microenvironment, or the characteristics of the immune cells, extracellular matrix, blood vessels, fibroblasts, and other entities in the area in which the tumor sits. Much of this work entails collaborations within the vet school as well as reaching across schools to fold in diverse expertise.

Cells image from the Fuchs laboratoryDr. Serge Fuchs, Professor of Cell Biology, is one such researcher. In collaboration with fellow Penn Vet researchers such as Puré, he has examined the so-called “stromagenic switch,” the process whereby normal fibroblasts morph into cancer-associated fibroblasts that permit, support, and protect the growth and spread of cancer cells. His work has further progressed through collaboration with the researchers at the Perelman School of Medicine, including Dr. Constantinos Koumenis, Professor of Radiation Oncology, and Dr. Sandra Ryeom, Associate Professor of Cancer Biology, among others. He is hopeful that a focus on translational medicine, facilitated by the Cancer Center, will help shed light on the nuances that distinguish animal from human cancers.

Dr. Susan Volk“My view is that comparative oncology has huge potential in serving human oncology,” Fuchs said. “We have to do more than take the human drugs and see if they work in a veterinary population. We have to innovate to create something that will work for humans and hopefully for pets as well.”

The work of another Cancer Center member, Dr. Susan Volk, Assistant Professor of Small Animal Surgery at Penn Vet, is influenced by her experience in the clinic. “Front of mind, for me, is how I can make a difference in my patient population,” she said. Having initially studied wound healing, she discovered that a protein called type III collagen helps in the healing process and also prevents the spread of tumors. Through partnerships with researchers such as Dr. Robert Mauck of Penn Medicine and the School of Engineering and Applied Science, as well as Dr. David Chenoweth of the School of Arts & Sciences, she’s been working on designs for biomaterials to be used after removing tumors to prevent local recurrences of cancer.

“Having the resources from around Penn allows us to combine efforts, not only with the medical and veterinary schools, but also with engineers and chemists. We can leverage all the information and knowledge to push forward in our understanding of cancer,” Volk noted.

Dr. Karin Sorenmo with Brownie, a shelter dogs enrolled in the Penn Vet Shelter Canine Mammary Tumor Program. Brownie was the program’s 100th dog in 2013.In a particularly fruitful partnership with Dr. Karin Sorenmo, Professor of Oncology, Volk is deepening her investigation into the role of the tumor microenvironment in dogs through the Penn Vet Shelter Canine Mammary Tumor Program. This endeavor, which Sorenmo leads, treats shelter dogs who develop mammary tumors—a more common occurrence in unspayed female dogs. The dogs, in turn, provide a robust study sample for the researchers to tease out the role of the tumor microenvironment, environmental risk factors, tumor histology, and hormone-dependence in influencing the risk of metastasis. Because dogs often have multiple tumors in various stages, from benign to malignant, they allow researchers to examine the changes that occur as cancer arises and progresses, which cannot be done in human patients.

“I realized that with these dogs, we have an excellent way to study breast carcinogenesis,” Sorenmo explained. “This program allows us to do two good things: We can save dogs, and we can make some really important strides with research.”

Still more Penn Vet faculty are contributing their expertise to the Center. Dr. Christopher Lengner, Associate Professor of Biomedical Sciences, is using technologies like CRISPRCas9 and organoids to explore mechanisms of colon cancer progression (read more about his research here).

The Lengner laboratory is studying the deletion of a tumor suppressor gene called APC, whose loss is thought to initiate the vast majority of colorectal cancers.Dr. Nicola Mason, Associate Professor of Medicine and Pathobiology, has ties to Penn Medicine dating back to her postdoctoral research with immunotherapy pioneer Dr. Carl June. She has built a productive research portfolio by capitalizing on the immune system’s ability to attack cancer (read more about her research here). In addition to continuing a collaboration with June focused on osteosarcoma, a disease that affects children as well as dogs, she’s also been part of a multi-year collaboration with Dr. Robert Vonderheide, the new director of the Abramson Cancer Center (ACC), on lymphoma immunotherapies.

Many Species, One Health

Penn Vet—which lists 10 of its faculty as members of Abramson Cancer Center—has long had a close relationship with Penn Medicine. Now the Vet Cancer Center can serve as a complementary unit to ACC, and vice versa, to provide insights and translational discoveries that neither center could accomplish alone.

“This new effort builds on a long history of collaboration between the Abramson Cancer Center and the School of Veterinary Medicine,” said Vonderheide, who is also the John H. Glick Abramson Cancer Center’s Director Professor. “That collaboration has manifested in very impactful translational research projects, including several focused on immunology. It has become very clear what one can learn from privately owned dogs and cats that develop cancer and how one can accelerate collaborative research to benefit both animal and human medicine. The Vet Cancer Center is a statement that we want to take that progress to the next level.”

Puré, who joined Penn Vet four years ago from appointments at the Wistar Institute and Penn Medicine, is a firm believer in such partnership and cross-pollination, having engaged in a number of collaborative projects in pursuing her research into the role of stromal cells and the extracellular matrix in inflammation and cancer.

Dr. Oliver GardenPuré’s emphasis on translational work has helped mobilize enthusiasm and resources within the School to support an integrated approach to cancer. This has been magnified by the recent appointment of Dr. Oliver Garden—a clinician with a deep interest and practice of laboratory research—as new Chair of the Department of Clinical Sciences and Advanced Medicine.

“I see the Cancer Center as a pivotal center of gravity for cancer research,” Garden said, adding that the Center is “a beautiful way of ensuring concordance of thinking between fundamental researchers in Biomedical Sciences, and my own department.”

Since coming to Penn Vet late last year, Garden has reached out to researchers across the University to collaborate on innovative projects—such as a biobanking initiative to collect lymphoma samples in dogs, working with Dr. Megan Lim and Dr. Kojo Elenitoba-Johnson of Penn Medicine.

“That project will be a model of One Health, looking at the disease in humans as well as veterinary species,” he noted. “We need to understand more about the mechanisms of cancer and how it arises, oncogenesis in other words, and also biomarkers and novel diagnostic methods, as well as new ways of prognosticating and delivering care for cancer patients.”

Tools for Progress

In addition to fostering collaborations, the Center will be launching a campaign to build infrastructure and recruit personnel in order to support its mission. A major component will be the creation of a Veterinary Therapeutics Laboratory, or Penn Vet Lab for short, where therapies will be modified to suit the needs of companion animals and the results tightly assessed.

“The Penn Vet Lab will enable us to get scientific information as to why a given therapy works or not, and then go back to the lab and inform an iterative process,” Puré says. “It will also monitor responsiveness to therapy and do a mechanistic readout of why drugs do or do not work.”

The Lab will help generate revenue for research as well, making it “an asset to the School,” said Sarah Rauers, administrative coordinator for the Cancer Center. “New discoveries made in the lab can be licensed and clinical trials paid for by pharmaceutical companies, grants, and foundations.”

The Puré laboratory has produced an image of a pancreatic ductal adenocarcinoma tumor, established using orthotopic implantation into mice.Added Puré, “This way, a client won’t be covering the full cost of a clinical trial, but we’ll still be developing new reagents, making adaptations, and hopefully informing cancer therapies for humans as well.”

In addition, Garden and Puré hope to hire one or two new faculty members with a focus in cancer biology and possibly radiation therapy. They’re also aiming to build up a cancer unit in the Veterinary Clinical Investigation Center, hiring new nursing staff that will dedicate energy to running tests on new cancer therapies.

All told, the Cancer Center will build upon Penn Vet’s already strong and varied expertise in cancer, from the lab to the clinic—helping unify, streamline, and accelerate progress to find therapies and cures in a disease that affects so many animal and human lives.

According to Puré, “It’s about people collaborating, bringing truly complementary expertise and ideas to build a much more concerted effort to attack the problem.”

Cancer Research is a Campus-Wide Endeavor

The Penn Vet Cancer Center is joining a host of other major efforts around the University that are harnessing the campus’s formidable scientific expertise in the fight against cancer. Most notably, the Perelman School of Medicine’s Abramson Cancer Center (ACC) provides a home for world-class research, care, and education. ACC counts among its members hundreds of researchers—including nearly a dozen faculty from Penn Vet—who work tirelessly to uncover the mechanisms that underlie cancer’s progression and find ways to stop it.

Robert Vonderheide is ACC’s director and an internationally renowned expert in cancer immunotherapy who has pioneered new strategies for treating pancreatic cancer, melanoma, breast and ovarian cancers. According to him, part of the strength of ACC comes from the diversity of voices on campus to support it. “You have CHOP [Children’s Hospital of Philadelphia], the medical school, the vet school, and more, all on one campus,” he said. “That allows us to have these amazing collaborations and innovative discussions in adult health, pediatric health, and veterinary health. I would say this is something really unique to Penn.”

Former Vice President Joe Biden with Penn Medicine’s Drs. Bruce Levine and Carl June and Penn President Dr. Amy Gutmann.Perhaps it’s not a surprise, then, that former Vice President Joseph Biden kicked off his “moonshot” to cure cancer in early 2016 with a stop at Penn. Meeting with experts including Penn Medicine’s Drs. Carl June and Bruce Levine, Biden praised the University’s progress, particularly in immunotherapy. “You’re on the cusp of some breakthroughs,” he noted.

In addition to scientific innovation, Penn is embracing new approaches to how that research gets done. A prime example is the Parker Institute for Cancer Immunotherapy, which launched in 2016 thanks to a $250 million gift from philanthropist Sean Parker. The Parker Institute unites Penn with five other leading medical schools and cancer centers to
accelerate breakthroughs in immunotherapies. Its unique research model encourages cross-institute collaboration to speed the translation of basic research to the clinic.

With its pioneering, cross-species work—and new Cancer Center—Penn Vet will continue to be a key partner in contributing to the University’s progress toward beating this disease.