ACSL4: biomarker, mediator and target in quadruple negative breast cancer

Breast cancer is a heterogeneous disease for which effective treatment depends on correct categorization of its molecular subtype. For the last several decades this determination has relied on hormone receptor status for estrogen, progesterone and HER2. More recently, gene expression data have been generated that further stratify both receptor-positive and receptor-negative cancers. The fatty acid-activating enzyme, ACSL4, has been demonstrated to play a role in the malignant phenotype of a variety of cancers, including breast. This lipid metabolic enzyme is differentially expressed as a function of subtype in breast tumors, with highest expression observed in the mesenchymal (claudin low) and basal-like subtypes. Here we review data that support the potential of utilizing ACSL4 status as both a biomarker of molecular subtype and a predictor of response to a variety of targeted and non-targeted treatment regimens. Based on these findings, we suggest 3 expanded roles for ACSL4: 1. as a biomarker for classification of breast cancer subtypes; 2. as a predictor of sensitivity to hormone-based and certain other therapies; and 3. as a target for the development of new treatment modalities.