Researchers may have discovered a new therapeutic target for patients with breast cancer—the TONSL gene—while attempting to understand the mechanisms behind breast cancer cell pathogenesis, according to a novel study published by Khatpe et al in 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,” explained senior study author Harikrishna Nakshatri, BVSc, PhD, the Marian J. Morrison Professor of Breast Cancer Research in the Department of Surgery and Professor of Biochemistry and Molecular Biology in the School of Medicine as well as Associate Director of Education at the Vera Bradley Foundation Center for Breast Cancer Research at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center. “The…initial step in [the development of] 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,” he added.
Study Methods and Results
“When comparing healthy breast tissue and cancerous cells, we wanted to find out…the earliest genomic change that happens to initiate the cancer,” Dr. Nakshatri noted. “In that process, we identified a gene called TONSL that can make breast cells proliferate indefinitely,” he highlighted.
In the new study, Dr. Nakshatri and his colleagues used healthy breast cells to analyze the earliest chances in these cells as they became cancerous—and found that the TONSL gene may be amplified in about 20% of patients with breast cancers and more than 30% of those with metastatic breast cancer.
The researchers revealed that the TONSL protein works with other proteins—including one called FACT. In the breast cancer models they created with the TONSL amplification, they discovered that breast cancer cells were highly susceptible to the existing curaxin-based agent CBL0137, which targets the FACT complex.
Conclusions
“Breast cancer is a diverse disease with different subtypes, and some patients respond to the different treatments, and others do not. With 20% of breast cancer patients having amplification of this gene, more research is very important to target TONSL,” emphasized lead study author Aditi Khatpe, a PhD candidate at the Indiana University School of Medicine. The researchers hope their new findings can lead to the development of novel therapeutics for patients with breast cancer.
Disclosure: The research in this study was supported in part by the Catherine Peachey Fund and the Vera Bradley Foundation for Breast Cancer. For full disclosures of the study authors, visit aacrjournals.org.
