Abstract

Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype to treat because of its heterogeneity and lack of specific therapeutic targets.

In this review we offer an overview of the strategies that have been exploited to counteract HMGA chromatin architectural factors activities in breast cancer and in particular in TNBC. Different strategies have been exploited; these involve interfering with their nucleic acid binding properties and the blocking of HMGA expression and some approaches have provided promising results. However, some unique characteristics of the HMGA proteins have not been exploited; these include their extensive protein-protein interaction network and their intrinsically disordered status that present the possibility that HMGA proteins could be involved in the formation of proteinaceous membrane-less organelles by liquid-liquid phase separation. These unexplored characteristics could open new pharmacological avenues to counteract the oncogenic contributions of HMGA proteins.