Triple-negative Breast Cancer: Identification of circRNAs With Efficacy in Preclinical In Vivo Models

Ulrich H Weidle, Fabian Birzele

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with insufficient options for therapy. In order to identify new targets and treatment modalities we searched the literature for circular RNAs (circRNAs) which mediate efficacy in TNBC-related in vivo preclinical models. In addition to 5 down-regulated circRNAs which modulate tumor-suppressive pathways, we identified 15 up-regulated circRNAs. Down- and up-regulated refers to expression in corresponding non-transformed cells and tissues. The up-regulated circRNAs comprise five transmembrane receptors and secreted proteins as targets, five transcription factors and transcription-associated targets, four cell-cycle related circRNAs and one involved in paclitaxel resistance. In this review article we discuss drug-discovery related aspects and modalities of therapeutic intervention. Down-regulated circRNAs can be reconstituted by re-expression of corresponding circRNAs in tumor cells or up-regulation of corresponding targets. Up-regulated circRNAs can be inhibited by small-interfering RNA (siRNA) or short hairpin RNA (shRNA)-based approaches or inhibition of the corresponding targets with small molecules or antibody-related moieties.