Androgen blockade based clinical trials landscape in triple negative breast cancer

Abstract

Androgen receptor (AR) targeted treatment has shown promising preliminary results in triple negative breast cancer (TNBC). Identification of AR-associated signaling pathways is of great significance for in-depth understanding of their roles in pathogenesis of TNBC. To meet this objective, preclinical and clinical studies were conducted to clarify the biological interactions of AR signaling and combination strategies based on AR-targeted therapy. Biologically, AR signaling in TNBC which not only interacts with a network of key pathways, involving PI3K/AKT/mTOR, cell cycle, and DNA damage repair pathways, but mediates pivotal processes of tumor initiation and immunogenic modulation, may present an opportunity to overcome the insensitivity of single AR-targeted therapy. Research in investigating androgen-blockade based combination therapy in this aggressive tumor has demonstrated promising benefit in preclinical studies, and comparable clinical trials of combined strategies with CDK4/6 inhibitors, PI3K inhibition, chemotherapy, and immunotherapy, are ongoing. Accordingly, clinical interpretation of AR-related biological interactions, aiming at combined blockade of the signaling pathways may pave a new way for endocrine-based therapy in the treatment of TNBC.

Keywords: Androgen; Breast; Combination; Receptor; Triple.