New Therapeutic Targets for Triple-Negative Breast Cancer Discovered

Researchers may have identified potential new drug targets to treat patients with triple-negative breast cancer (TNBC).

TNBC is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and hormone epidermal growth factor (HER2)-negative, and thus doesn't respond to hormone therapies. It is even more difficult to treat once is has metastasized.

The targets are long noncoding RNAs (lncRNA) that interact with hypoxia-inducible factor 1 (HIF-1), a signaling pathway that is overexpressed in different cancers. Cell signaling pathways are the chain of events that can either slow down or speed up disease progression. HIF-1 is able to regulate breast cancer progression.

First published  in Nature Cell Biology, this study was led by scientists at The University of Texas MD Anderson Cancer Center who worked with several insititutions worldwide that were focused on HIF-1’s role in TNBC. The teams analyzed data from The Cancer Genome Atlas (TCGA), a research program supported by the National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) within the National Institutes of Health (NIH) that studies genomic changes in more than 20 different types of cancer.

In cancer cells, small changes in the genetic letters can change what a genomic word or sentence means. A changed letter can cause the cell to make a protein that doesn’t allow the cell to work properly. These proteins can make cells grow quickly and damage nearby cells. The genome of a cancer cell can differentiate one type of cancer from another and also identify a subtype of cancer within that type.

Liquing Yang, PhD and co-author Chunru Lin, PhD, both assistant professors in the Department of Molecular & Cellular Oncology, confirmed four sites for phosphorylation, a process that turns protein enzymes off and on, which has an effect on key cellular functions.

“Our study identified four previously unknown phosphorylation sites in a LINK-A [long intergenic noncoding RNA for kinase activation] regulated signaling pathway,” Dr. Lin said in an MD Anderson press release. “These events predict a worse outcome in TNBC patients suggesting that the LINK-A pathway plays a critical role in this disease and may provide wide-ranging therapeutic treatment targets.”

Dr. Yang suggests that LINK-A and LINK-A interacting kinases and receptors are promising therapeutic targets for TNBC.

This aggressive form of breast cancer does not yet have many effective treatments, so this finding may be very promising for patients.