Director of new Women’s Health Program at TGen believes teamwork is key to defeating cancer
Dr. Andrea Bild, who recently became the first major joint recruit of the year-old affiliation between TGen and California’s City of Hope, aims to combat cancer using multidisciplinary teams that target a cancer’s common vulnerabilities.
Key to Dr. Bild’s research program is the realization that when patients no longer respond to initial treatments —when their cancer becomes resistant to certain drugs— there may remain a way to target the evolving cancer. Identifying characteristics (phenotypes) along the biological signaling pathways within cells, and studying the patterns of these potentially cancer-related phenotypes, might lead to new therapeutics.
“As a postdoc, and then later leading my own research team, I realized that we had to move beyond identifying mutations in tumors alone and that we should be using the more common phenotypes as information that can help treat patient tumors in an individualized manner,” she said.
From an initial Nature paper in 2006 (Oncogenic pathway signatures in human cancers as a guide to targeted therapies), which was the foundation for the phenotype analysis of tumors, up to a current Nature Communications paper published last month (Combating subclonal evolution of resistant cancer phenotypes), Dr. Bild is combating tumor phenotypes in the lab and in the clinic.
At TGen, Dr. Bild holds the titles of Professor, Integrated Cancer Genomics and Director of TGen’s new Women’s Health Program. At City of Hope, she is a Professor in the Department of Medical Oncology and Therapeutics Research.
Through her undergraduate training at the University of Florida and doctoral work at the University of Colorado, her academic focus is trans-disciplinary as a pharmacologist and systems biologist. Her inclination has always been the translational effort of moving laboratory discoveries as soon as possible to patients.
She understands the need — in complicated inquiries — to assemble a band of experts in a variety of fields: from physicians to clinicians, pathologists, biologists and bioinformaticians.
And did we mention fun?
“When there’s opportunities on complex problems like this, the way you bring people together is finding those who share your interests, and have the skillsets needed,” she said, “and then making it fun for everyone to work together.”
Dr. Bild’s number one priority is helping the patient.
“For me, what that means is figuring out therapeutic strategies that either prevent (drug) resistance from developing, or combat a resistance state,” she said. “That’s my long-term objective.”
Center of HOPE
Dr. Bild brings with her a $9 million, 5-year grant that started in April from the National Cancer Institute (NCI) — a grant called the Center of HOPE (Heterogeneity Of Phenotypic Evolution). She could not have guessed when she named the grant that she would soon be working for a healthcare enterprise that also had “hope” in its name.
When she submitted her Center of HOPE grant application, she was still an Associate Professor of Pharmacology and Toxicology, and Director of the Genome Sciences Program at the University of Utah. It was there that she met Dr. Sunil Sharma (see cover story) an oncologist who specializes in gastrointestinal cancers, such as pancreatic cancer, but who also consults on a variety of cancers, including the type of breast and ovarian cancers that is the main focus of Dr. Bild.
Much of Dr. Bild’s work is tied to her membership in NCI’s Cancer Systems Biology Consortium, where she is a Principal Investigator of multi-institutional grants. Her team focuses on the development and application of genomic-based tools for cancer prevention and treatment. One defining method of her inquiries is to keep her research directly linked to the patients she is trying to help through the use of actual patient tumor samples, rather than cell lines.
“The foundation of our program is based on what happens in patient tumors so that we can ensure our research is relevant,” she said, “and so we’re able to use systems biology to track the complexity of evolving resistance states over the course of treatment. You can only get data that tells you exactly what is happening with the patient if you use tumor cells from the patient.”
The Mathematics of Precision Medicine
Dr. Bild also experiments with mathematical formulas as a way of probing new ways to attack cancer. It was a talk by Dr. Frederick Adler, a Harvard-Cornell-UC Davis-trained Professor of Mathematics and Biology at the University of Utah, which enticed Dr. Bild to study how the evolution of plants might help explain how cancer evolves and evades treatment.
In the analogy with plant ecology, subclones correspond to plant species, cells to individual plants (which have both a species and a phenotype), and the tumor to the entire community.
“How do populations of different plants interact with each other? How do plant populations survive when there’s other invasive species?” she said. “We now characterize single-cell phenotypes in patient tumors as they are emerging under the stress of therapeutics — chemotherapies — and use that data in models that, initially, were derived from plant biology.
“We’re using really innovative mathematical models taken from plant evolution to profile our patient tumor cells and identify vulnerable points at which we could use novel therapeutic strategies.”
It holds promise of breakthroughs by looking at cancer in ways no one else has tried before, though Dr. Bild says there are no guarantees: “We’re taking a completely new mathematical approach to problems. That could yield different ways of looking at these complex systems that haven’t been tried before. We hope it yields something meaningful.”
More than anything, she is excited to be working at TGen and City of Hope where she can apply her discoveries to patients.
“Given City of Hope’s strength in medical oncology, and TGen’s computational expertise,” Dr. Bild said, “we can lead the way in incorporating complex genomic information in drug treatment decisions.”
