New potential therapeutic approach for HER2-positive breast cancer discovered

enzymatic activity were highest in ER-HER2+ breast cancer cell lines. Silencing of HER2 as well as inhibition of HER2 signaling decreased EDI3 expression. Inhibition of EDI3, in turn, primarily reduced the viability of ER-HER2+ cells. Furthermore, inhibition of EDI3 in ER-HER2+ cells resistant to HER2-targeted therapy reduced cell viability in vitro and tumor growth in vivo in mice.

Based on these findings, the researchers conclude that EDI3 expression is upregulated in ER-HER2+ breast cancers compared to other subtypes. Furthermore, inhibiting EDI3 leads to a significant reduction in viability and tumor growth, especially in ER- HER2+ breast cancer cells that are resistant to conventional HER2-targeted therapies. Targeting EDI3 may therefore be a therapeutic approach to enhance the effect of standard therapies, or an alternative in the case of resistance to standard therapies.

Receptor status of the tumor

HER2 is the name of a growth factor receptor. Its task is to take up signals from outside the cell, conduct them into the cell interior, leading to the stimulation of cell division. If a patient has too much of the HER2 growth factor receptor, the tumor is referred to as HER2+—a subtype of breast cancer. As a result of the many growth signals, the tumor can divide uncontrollably. Determining HER2 status is important since there are medications that specifically target HER2. Most HER2+ patients do respond successfully to such medications, but therapy resistance is a problem for some. Therefore, alternative treatments are needed for this tumor subtype.

In addition to HER2 signaling, the hormone estrogen can also affect the growth of breast cancer cells. Estrogen attaches to binding sites (hormone receptors) of the cell, which then turns on expression of genes that favors cell growth. To determine whether a tumor grows in a hormone-dependent manner, the proportion of cells and the amount of the corresponding hormone receptors is often examined. The result is expressed by the indication ER+ (estrogen receptor positive) or ER- (estrogen receptor negative).

More information:
Magdalena Keller et al, Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+ breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth, Journal of Experimental & Clinical Cancer Research (2023). DOI: 10.1186/s13046-022-02578-w

Provided by
Leibniz Research Centre for Working Environments and Human Factors in Dortmund