This Philly Cancer Center Is Overturning Our Basic Understanding of Cancer with Its Insight into the Field of Epigenetics
In the public consciousness, the mystery of cancer is often boiled down to a simple question of how to destroy bad cells while saving good cells. The solution to this mystery often seems just outside the reach of conventional treatments.
But in just the past few decades, a quiet revolution is underway in cancer care. It promises to displace that oversimplified and blunt narrative with a more hopeful one, where a new understanding of the nature of cancer yields better treatment. This revolution centers on a term that may soon become commonplace: epigenetics.
“Chemotherapy was really developed to target and essentially destroy DNA so the cell would die,” Margaret von Mehren, MD, chief of Fox Chase’s Sarcoma Medical Oncology program, says. “It’s not a very specific way of trying to kill the cancer. We’ve since gotten more sophisticated. What we’re talking about now is really targeting a process that the cells use to regulate which genes are turned on or turned off. That process is called epigenetics or epigenetic control.”
Being able to essentially turn off the problematic processes of cancer — like hitting a “light switch,” in von Mehren’s words — seems like the stuff of science fiction. Of course, making this a reality is complex; there is an entirely new network of challenges to solve. But for a groundbreaking group of researchers and physicians in Philadelphia at the forefront of cancer care, epigenetics represents a very real step down the path that promises to wholly change our relationship with cancer treatment.
Dr. von Mehren — who treats one of the most challenging cancers to understand — is seeking to turn off the switch for her patients by working with that group, Fox Chase’s Cancer Epigenetics Institute (CEI), founded just this year as a unique interdisciplinary team led by Johnathan R. Whetstine, PhD. Combining knowledge from across the spectrum of cancer research and care, the CEI is seeking to aid physicians like von Mehren by unlocking and accelerating the full power of epigenetics. In doing so, they could create a new paradigm for cancer care.
Solving the Most Difficult Mystery
Dr. von Mehren will tell you that the condition she studies and specializes in treating — sarcomas, rare cancers that develop in the bones and soft tissues — are not by any means the most widespread.
“These are exceedingly rare cancers in the United States, including pediatrics and adults,” von Mehren says. “They represent less than 20,000 cases diagnosed each year altogether so they’re very rare, which makes it a challenge to conduct clinical research because of the small numbers of patients.”
But that didn’t stop von Mehren from dedicating her life to it. To discuss the initiation of one of the most groundbreaking trials that changed the face of sarcoma treatment 21 years ago, she left her honeymoon in Canada to travel to New Orleans to meet with her co-investigators.
“It was kind of a bittersweet ending to our honeymoon that way, but it was very exciting,” von Mehren says.
The number of people impacted by the disease doesn’t affect von Mehren’s passion for finding a successful treatment; of course, that holds true for her patients as well.
Dorothy Keisling knows that firsthand. In November 2019, she was diagnosed with Ewing sarcoma. Recalling the successful treatment a friend of hers received years before at Fox Chase, Keisling sought treatment at Fox Chase Cancer Center. Under the guidance of Dr. von Mehren and her team, Keisling received five different chemotherapy drugs, as well as radiation. And now, as a result of these efforts, Keisling is officially a cancer survivor.
“I had such confidence in Dr. von Mehren,” Keisling says. “She was always checking in and explaining the advancements Fox Chase has made in sarcoma treatment.”
What Keisling didn’t realize at the time, and what makes her story not just a happy story, but an amazing one from a scientific perspective, is that she luckily had come to a cancer center specializing in the treatment of this rare cancer. And now, thanks to Fox Chase’s epigenetics approach, more advances are on the horizon.
The Final Frontier
“There’s an entire universe to be found,” Whetstine says, in reference to epigenetics. The field, in Whetstine’s explanation, holds inestimable opportunities for cancer research. Instead of targeting and destroying cells, epigenetics seeks to change the way DNA is organized and the way genes are expressed, thereby changing the behavior of the cancer cells with the goal of making them more vulnerable to treatment.
That helps physicians like von Mehren, as well as specialists in more widespread cancers, in several ways. For one, as a result of the new paradigm, a whole new array of solutions are rapidly being discovered and implemented, which gives way to certain revolutionary combinations of treatments.
Because epigenetics doesn’t focus on the specific genetic code of a tumor, solutions aren’t limited to a specific type of cancer (breast cancer or colon cancer, for example). They have the potential to apply to a broad range of cancers.
“For example, we discovered a critical role for an epigenetic enzyme in cancer,” Whetstine says. “This discovery gave way to new research into ovarian cancer. When we started studying more carefully, it brought us to triple negative breast cancer. That then brought us to lung cancer, and then that brought us to neuroblastomas in kids. You follow leads and mechanisms and that cuts across cancer types.”
Since epigenetic processes impact multiple cancer types, researchers like von Mehren are able to apply that knowledge to rare cancers such as Ewing sarcoma, while oncologists’ treatment of more widespread cancers also benefit from the knowledge and discoveries. The cross-disciplinary approach and clinical trial expertise that brings researchers and physicians together at Fox Chase and the CEI has a critical compounding effect.
Patients at Fox Chase are able to experience breakthrough combinations in real time, while each treatment adds meaningfully to the toolkit of physicians and researchers who may have never interacted in a different environment. Dr. Whetstine’s epigenetic insight facilitated Dr. von Mehren to initiate a new clinical trial because of their ability to simply walk down the hall and speak to one another.
“We’re committed to trying to find new cancer therapies, and we do that with clinical trials,” von Mehren says. That is one of the biggest missions that we have as part of the Cancer Center. Because of the people and infrastructure at Fox Chase, we have a leg up.”
“I’m so proud to be a part of a place,” Whetstine adds, “where I’m empowered to facilitate the use of laboratory discoveries to make dreams come true in the clinic.”This is a paid partnership between Fox Chase Cancer Center and Philadelphia Magazine's City/Studio