Researchers Identify New Target for Breast Cancer Treatment

Researchers at the Vera Bradley Foundation Center for Breast Cancer Research at Indiana University Melvin and Bren Simon Comprehensive Cancer Center have uncovered a novel target for breast cancer treatment while seeking to understand what causes breast cells to become malignant.

“When comparing healthy breast tissue and cancerous cells, we wanted to find out what is the earliest genomic change that happens to initiate cancer,” said Harikrishna Nakshatri, Ph.D., the Marian J. Morrison professor of breast cancer research at IU School of Medicine and a researcher with the Vera Bradley Foundation Center for Breast Cancer Research at the IU Simon Comprehensive Cancer Center. “In that process, we identified a gene called TONSL that can make breast cells proliferate indefinitely.”

Nakshatri and his colleagues discovered that the TONSL gene is amplified in approximately 20% of breast cancers and more than 30% of metastatic breast cancers. They used healthy breast cells from the IU Simon Comprehensive Cancer Center’s Komen Tissue Bank to study the initial alterations in healthy cells as they turn malignant.

Their findings, “TONSL Is an Immortalizing Oncogene and a Therapeutic Target in Breast Cancer,” were published this week in the journal Cancer Research.

“Most of the cancer research to date is focused on understanding what happens when cancer progresses, but the earliest event that leads to cancer initiation has been the hardest to figure out,” Nakshatri said. “The very initial step in cancer is that these cells gain the ability to proliferate, and that’s the very first step that we have been able to make in models using tissue from the Komen tissue bank.”

According to Nakshatri, the TONSL protein interacts with other proteins, including one termed FACT. The breast cancer models developed by his team using the TONSL amplification were especially vulnerable to an existing medication that targets the FACT complex. Researchers are now hoping that their findings can be used in future breast cancer treatment.

“Breast cancer is a diverse disease with different subtypes, and some patients respond to the different treatments, and others do not. With 20 percent of breast cancer patients having amplification of this gene, more research is very important to target TONSL,” said Aditi Khatpe, first author of the paper and an IU School of Medicine doctorate student.

Khatpe, a cancer center trainee in Nakshatri’s lab, received the AACR-Sanofi Scholar-in-Training Award for the research abstract highlighting these findings. She presented the research poster at the American Association for Cancer Research (AACR) 2023 Annual Meeting this week.

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