OncoTargets and Therapy (Apr 2023)
Potential Therapeutic Targets for Luminal Androgen Receptor Breast Cancer: What We Know so Far
Abstract
Stefania Stella,1,2 Federica Martorana,1,2 Michele Massimino,1,2 Silvia Rita Vitale,1,2 Livia Manzella,1,2 Paolo Vigneri1,2 1Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; 2Center of Experimental Oncology and Hematology, A.O.U. Policlinico “G. Rodolico - San Marco”, Catania, ItalyCorrespondence: Stefania Stella, University of Catania, Department of Clinical and Experimental Medicine, Center of Experimental Oncology and Hematology, A.O.U. Policlinico “G. Rodolico - San Marco”, Via S. Sofia, 78, Edificio 8D/2, Catania, Italy, Tel +39 95 378 1946, Email [email protected]; [email protected]: Luminal Androgen Receptor Breast Cancers (LAR BCs) are characterized by a triple negative phenotype and by the expression of Androgen Receptor (AR), coupled with luminal-like genomic features. This unique BC subtype, accounting for about 10% of all triple negative BC, has raised considerable interest given its ill-defined clinical behavior and the chance to exploit AR as a therapeutic target. The complexity of AR activity in BC cells, as revealed by decades of mechanistic studies, holds promise to offer additional therapeutic options beyond mere AR inhibition. Indeed, preclinical and translational evidence showed that several pathways and mediators, including PI3K/mToR, HER2, BRCA1, cell cycle and immune modulation, can be tackled in LAR BCs. Moving from bench to bedside, several clinical trials tested anti-androgen therapies in LAR BCs, but their results are inconsistent and often disappointing. More recently, studies exploring combinations of anti-androgen agents with other targeted therapies have been designed and are currently ongoing. While the results from these trials are awaited, a concerted effort will be needed to find the biological vulnerabilities of LAR BCs which may disclose new and effective therapeutic targets, eventually improving patients’ outcomes.Keywords: triple negative breast cancer, luminal androgen receptor breast cancer, androgen receptor, targeted therapy, clinical trials
