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Triple-negative breast cancer (TNBC) is an aggressive form of disease that makes up about 10-15% of all breast cancers, according to the American Cancer Society. Because these tumors grow faster, and there are limited treatment options, patient outcomes are worse compared to other types of breast cancer.

Chuck Harrell, Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, was recently awarded a $1.7 million R01 grant from the National Cancer Institute to identify targeted drugs that can overcome chemotherapy resistance and effectively treat TNBC.

“The uncontrolled growth, or metastasis, of breast cancer cells in vital organs is responsible for the vast majority of breast cancer deaths that happen each year in the United States,” said Harrell, who is also an assistant professor in the Department of Pathology at the VCU School of Medicine. “The long-term goal of this research is to provide targeted treatment options for a group of patients that currently has extremely poor prognosis.”

Chemotherapeutics are used for the majority of patients with TNBC. Carboplatin is a chemotherapy drug commonly used in combination with other drugs to treat breast cancer. In many cases, advanced tumors can build up a resistance to carboplatin and render it ineffective. Using tissues taken from breast cancer patients and implanted into mice, Harrell will develop different types of tumor models that are sensitive to and resistant to chemotherapy. He will then perform genetic comparisons of the models’ DNA to identify biological pathways that have been altered when the cancer becomes resistant to chemotherapy. Once discovered, Harrell can target those pathways with different drugs to identify novel treatments that can overcome resistance to chemotherapy and kill TNBC cells.

There is a protein called epidermal growth factor receptor (EGFR) that is commonly overexpressed in TNBC. In some tumors, inhibiting the function of this protein may kill cancer cells; whereas, in other tumors different proteins keep the cells alive. This five-year grant will serve to identify biological pathways that can be targeted in combination with the EGFR protein to promote cancer cell death.

Harrell anticipates this grant funding, which is effective through June 2025, will help to rapidly determine new therapeutic combinations that can be tested through Massey-supported clinical trials.

“At the completion of this project, we hope the results can immediately translate to the clinical setting and provide new options for cancer patients with metastatic disease,” Harrell said.

Harrell is collaborating on this research with Mikhail Dozmorov, Ph.D., and Jason Reed, Ph.D., members of the Cancer Molecular Genetics research program at Massey, and Amy Olex, M.S., of the C. Kenneth and Dianne Wright Center for Clinical and Translational Research at VCU.

Written by: Blake Belden