Understanding One Gene’s Role in Cancer

September 16, 2013—The identification of cancer-associated genetic changes has paved the way for the development of highly targeted treatments. Biology major Kamil Lupicki (C’14) is currently researching one gene to gain a better understanding of its implications in triple-negative breast cancer.

“Cancers are a very diverse and complex group of diseases,” Lupicki said. There are not only subtypes of breast cancer; some of those subtypes have their own sub-subtypes. Sponsored by a Zukowski-Kolleng Undergraduate Research Scholarship, Lupicki spent the past summer studying triple-negative breast cancer (TNBC), a subtype of breast cancer that accounts for 10–20 percent of all breast cancers.

Lupicki, who is also a pre-med student, began his work on TNBC as a research assistant for Assistant Professor of Oncology Luciane Cavalli at the Georgetown Lombardi Comprehensive Cancer Center. “Breast cancers have traditionally been classified based on the expression of estrogen receptor (ER), progesterone receptor (PR), and the [overexpression] of human epidermal growth factor receptor 2 (HER2),” Lupicki explained. “In ER-, PR-, or HER2-positive breast cancers, the expression or overexpression of these proteins by the cancer cells can result in mechanisms that promote their growth or proliferation.”

Understanding the differences in marker expression in each subtype plays an important role in treatment. “Treatment options for [breast] cancers are significantly dependent on the expression of the ER, PR, and HER2 markers,” Lupicki said. Triple-negative breast cancers, however, do not express any of these three makers. TNBC is often considered an aggressive disease, with a high probability of reoccurrence within five years of diagnosis. Without specialized treatment, TNBC patients are left with more general options such as chemotherapy.

Working with Dr. Cavalli, Lupicki has focused on the BP1 homeobox gene, which was “amplified and correlated with a poorer prognosis” in a number of clinical cases. “We thought perhaps that this gene could be a molecular target for therapies in the future,” he continued. Creating a new drug treatment, Lupicki said, takes about 15 years. But each new drug must start with the question, “Where do we target treatment?”

With that question in mind, Lupicki began comparing the clinical case results to the TNBC cell lines, cancer samples available to researchers worldwide. The project gave him the opportunity to learn new research skills and gain experience conducting two well-known procedures: array-CGH analysis and fluorescence in situ hybridization (FISH) analysis. “I had a sense of what the research methods were from my biology and genetics classes,” he said. “[But] until I got into the lab, I didn’t realize how long some of the processes take, what their full procedures are, and how many times they don’t work.”

Using these procedures, Lupicki has been investigating DNA copy number changes in 18 TNBC cell lines, both on a global level and specifically with regard to the BP1 and HER2 genes. “These data will allow us to classify the TNBC cell lines with respect to the BP1 gene and explore whether BP1 can serve as an important molecular marker for aggressive TNBCs,” Lupicki said.

He acknowledged that working in a research lab often creates more questions than answers. After identifying the BP1 gene as a possible target for treatment, researchers will then need to identify what specific cellular mechanisms to target. Lupicki is still collecting data from this summer, but he plans to continue his work on BP1 and TNBCs this year as his Research Intensive Senior Experience (RISE) project.

“My end goal would be to have a more complete story of the BP1 gene: DNA amplification, the RNA levels, and the protein expression,” he said. “If I can do that, I think that would be great.”

—Elizabeth Wilson