Gene expression analysis helps identify genes that cause endocrine resistance in breast cancer

The most prevalent type of cancer detected in women is breast cancer (BC). BC is the second biggest cause of death among female cancer patients globally.

Video Credit: Oncotarget

Endocrine therapy is an effective treatment option for estrogen receptor-positive (ER-positive) breast tumors. However, ER-positive cancers can develop resistance to endocrine therapy in many situations, and tumor recurrence can occur following treatment. While some genetic abnormalities play a role in resistance in some patients, the root causes of endocrine therapy resistance remain mostly unknown.

“Endocrine therapies have been successful at improving cancer outcomes; however, the development of endocrine resistance, or resistance to inhibition of ER actions, remains a roadblock in breast cancer treatment,” the researchers said.

Scientists from UTHealth Houston, the University of Chicago, the University of Texas MD Anderson Cancer Center, and the University of Houston investigated the dynamic behavior of the entire gene population to discover novel genes involved in the development and growth of endocrine-resistant breast cancer.

“In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly changes during cell modeling of endocrine-resistant BC development,” the researchers said.

The scientists used information from a public functional genomics source to use their recently created statistical pipeline to further know the mechanism of obtaining endocrine resistance and its fundamental gene expression patterns. They discovered dynamically regulated genes involved in the development and evolution of endocrine resistance.

Using dynamic gene expression analysis, they discovered 34 new genes that shifted dramatically throughout the development of endocrine-resistant breast cancer in cell models. In a microarray study of endocrine-resistant and endocrine-sensitive tumor tissues, the expression of a subset of these genes was also differentially expressed.

Interestingly, a subset of those genes was also expressed differently in triple-negative breast cancer (TNBC) than in ER-positive breast cancer.

The researchers conclude, “The findings suggest shared genetic mechanisms may underlie the development of endocrine-resistant BC and TNBC.”