Finding Groundbreaking Ways to Flip the Switch on Cancer


vonMehren and Whetstine
As part of the Fox Chase Cancer Epigenetics Institute, Margaret von Mehren, MD, and Director Johnathan Whetstine, PhD, are working toward novel therapeutics that help control how cancer cells react to their environments.

Scientific Insights for Positive Patient Impact

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.

In 2021, Fox Chase launched a unique interdisciplinary collaborative called the Cancer Epigenetics Institute, a Philadelphia-based national hub for epigenetics study that focuses on the mechanisms promoting cancer and therapeutic resistance. With Dr. Johnathan Whetstine as the Founding Director, the group’s current membership of 22 elite researchers and physicians includes Dr. Margaret von Mehren, Chief of the Sarcoma Medical Oncology Division at Fox Chase.

In combining knowledge from across the spectrum of cancer research and care, the Institute’s mission is threefold. It starts with fostering bench-to-bedside discovery in cancer epigenetics through academic-to-industry and academic-to-academic partnerships. Next, the team aims to uncover critical mechanisms controlling cellular function and resistance so novel biomarkers and drug targets can be identified to reduce cancer-related morbidity and mortality.

Finally, Dr. Whetstine says, with one-third of the membership directly involved in clinical trials, the Institute is driven to leverage its discoveries and make a rapid clinical impact on patients: “If we see an opportunity, we will carry it to the finish line and make sure that it gets to our patients as soon as possible.”

“The whole objective is to shorten the gap of basic discovery to clinical impact with a focus on a topic that impacts all therapy types -- chemotherapy, immunotherapy, you name it, it has implications,” he adds.

The Role of Epigenetics in Cancer

In breaking down the meaning of epigenetics, “genetics” is the body’s DNA, and “epi” refers to the environment around it, which is what controls the DNA. As opposed to many cancer treatments that target and destroy cells, epigenetics seeks to change the way DNA is organized and the way genes are expressed, thereby modifying the behavior of the cancer cells with the goal of increasing their vulnerability to treatment.

Dr. Whetstine makes the analogy of a thermostat that can be turned up or down, or a circuit board with hardware that allows electricity to move through and where switches are turned on or off. Epigenetics works in a similar way as “information control,” which results in cells making decisions about what kind of cell they are – liver, skin, brain, cardiac, and so on. All the cells have the same DNA, but they don’t have the same environment around them.

That’s why epigenetics can potentially be a game-changer in fighting cancer. A cancer cell, using its DNA to deviate from what normal cells do, can turn on genes that support its growth or prevent it from dying. Through the understanding of epigenetics, clinicians and researchers aim to take control of that information: identifying and turning off genes that help a cancer cell survive better, or turning on genes that enable the cell to die.

“It literally is a fine-tuning tool,” Dr. Whetstine says.

The translational research goals focus on biomarkers for early detection of a range of cancers, risk assessment, predicting outcomes, biomarkers of specific drug response, preclinical studies, and clinical trials of epigenetic therapy. Because epigenetics doesn’t focus on the specific genetic code of a tumor, solutions aren’t limited to a specific type of cancer.

As such, clinicians like Dr. von Mehren are able to apply that knowledge to rare cancers, like within her specialization of sarcomas – driving the possible implementation of new drug combinations, or identifying which drugs to consider in certain patient populations. Oncologists who treat more widespread cancers also benefit from the discoveries.

“As medical oncologists, this collaboration allows us to incorporate science in what we do. Twenty years ago, we were very focused on transcription factors, tyrosine kinase inhibitors, tumor suppressors and so on – but we've come to appreciate that there is another higher order structure that is interplaying and interacting with all of those things, and that's epigenetics,” Dr. von Mehren says.

“In my field, which is a very narrow, rare tumor population, there are clear examples where we know there is involvement of epigenetics in the biology of tumors. Now we have the opportunity to use that biology to help control or eradicate the disease.”

Fox Chase’s Leadership in Innovative Research

The Cancer Epigenetics Institute is just another example of how the Fox Chase culture drives increased collaboration on new solutions for cancer in a close-knit, patient-centric setting. The cross-disciplinary emphasis and clinical trial expertise that bring researchers and physicians together have a significant compounding effect.

“The people here want to be able to develop their own interesting, meaningful studies and ask questions about the next type of therapy that we’re going to be using and the next advantage that we can find for our patients,” says Dr. von Mehren. “To do that, the clinical side needs to interact with science to get the biologic insights to say this is where we need to shine a light to see if we can target this area, or can we disrupt this mechanism in this tumor.”

In fact, Dr. Whetstine’s epigenetics insights facilitated Dr. von Mehren to initiate a new clinical trial because of their ability to simply walk down the hall and start a conversation – which is truly representative of the collaborative spirit found among the members of the Institute and the people throughout Fox Chase.

“The truth is we're meeting in the same place because the ultimate goal is to see if we can transform care. That is just something that's here at Fox Chase – it’s an ethos that's palpable,” Dr. Whetstine says. “Whatever type of cancer it may be, the dynamic here allows us to bring basic science, tools and knowledge closer and faster clinically, which means we can get new trials, new drugs and new opportunities faster. That is the secret to this place that is magic.”

Research, Care, Community

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.  

Become Part of Tomorrow’s Cancer Care Today

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.

Interested in joining our world-class research team to advance the fight against cancer?

View Careers in Research →