Gaining Ground: Personal Losses Help Drive Pioneer in Stem Cell Study

Beth Fand Incollingo @fandincollingo
Published: Wednesday, Dec 12, 2012
Dr. Jenny C. Chang

Photo courtesy of Drew Donovan.

Jenny C. Chang, MB BChir, MD
Cancer took Jenny Chang’s aunts. It took her uncles. And it took her 9-year-old cousin.

In all, at least seven of her relatives died of cancer, and many of them stayed with Chang’s family as they underwent chemotherapy in the 1970s and the 1980s.

It was a troubling experience for a child.

“It was really grim,” recalled Chang, MB BChir, MD, now a renowned breast cancer oncologist and translational researcher. “In one sense, it was fascinating to understand that this alien could take over a body, even in a child, while, obviously, the human side was a tremendous suffering.”

Despite her youth and her family’s “hush-hush” attitude about the disease, Chang deduced that such suffering “could be alleviated–you just have to figure out what happened.” By the time she was 12, she had vowed to dedicate her career to doing just that.

Today, the 49-year-old physician is well on her way. As director of the Methodist Cancer Center at The Methodist Hospital in Houston, Texas, Chang treats patients with breast cancer and conducts laboratory research in an area she has pioneered: studying the mechanisms of cancer stem cells, also known as tumor-initiating cells (TICs)⎯which, her investigations have shown, can survive chemotherapy, radiation, or hormonal therapy, and then spark recurrences or metastases. To help translate that work into practice, Chang also investigates treatments designed to target those cells, and leads early-stage clinical trials of the drug candidates.

Paving the Way for New Therapies

Largely, the doctor’s work has helped change the direction of breast cancer research by identifying potential targets for new cancer therapies.

In addition to isolating and patenting a 493-gene signature of the cancer stem cells that drive the “claudin-low” molecular subtype of breast cancer, Chang found evidence that such cells can be quieted through the targeting of specific molecular pathways, including the Notch pathway.

Her studies have demonstrated that targeting insulin-like growth factor can fight resistance in triple-negative breast cancer; that activation of the PI3 kinase pathway is associated with trastuzumab resistance; and that hyperthermia sensitizes resistant cancer stem cells to radiation. Chang has also found promise in targeting the STAT3 oncogene, which helps renew TICs in tumors that overexpress the protein p-Stat3. Before the end of the year, she said, her team will launch clinical trials of a small molecule, C188, designed to target the oncogene.

The doctor is already in the clinic as an investigator of chloroquine, a “cheap, safe” 60-year-old malaria drug being repurposed for use in breast cancer, and of the gamma secretase inhibitor MK-0752, which targets TICs and is being tested in metastatic breast cancer. In a phase I/II study, MK-0752 “worked well in decreasing cancer stem cells,” the doctor said, and another trial is being planned.

In short, Chang is unraveling the mysteries of cancer drug resistance that have, for so long, baffled oncologists, researchers, and patients.

“We know so little, but we’re beginning to know a lot more, because with the ability of high-throughput transcriptors and different types of profiling, like Next-Gen sequencing, we can understand some of the pathways that drive the tumors,” Chang said. “Over the next 10 years, the amount of data we’ll know about cancer will just be exponential, and putting it into perspective in a clinically relevant way that impacts patients is where I’d like to focus, because I see it as the most important thing.”

Taking Cancer Center’s Helm

Chang has been conducting her research at The Methodist Hospital since October 2010, when she stepped into the role of director of its cancer center.

She made the move from Baylor College of Medicine, also in Houston, where she began as an assistant professor in 1999 and rose to the rank of professor. While the institutions were integrated when Chang joined Baylor, they are now independent of each other.

For Chang, the switch included moving her large lab–including about five PhDs and four technicians–to Methodist’s new building.

It has also meant becoming the force behind some big changes.

Probably the most major shift has involved establishing a clinical research program at the cancer center. When Chang came on board, there were phase III, pharmaceutical-driven studies being conducted there, but trials arising out of academic research are something new.

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