Steroid receptor coactivator-3 as a potential molecular target for cancer therapy

Steroid receptor coactivator-3 (SRC-3), also called amplified-in-breast cancer-1 (AIB1), is an oncogenic coactivator in endocrine and non-endocrine cancers. Functional studies demonstrate SRC-3 promotes numerous aspects of cancer, through its capacity as a coactivator for nuclear hormone receptors and other transcription factors, and via its ability to control multiple growth pathways simultaneously. Targeting SRC-3 with specific inhibitors therefore holds future promise for clinical cancer therapy.

We discuss critical advances in understanding SRC-3 as a cancer mediator and prospective drug target. We review SRC-3 structure and function and its role in distinct aspects of cancer. In addition, we discuss SRC-3 regulation and degradation. Finally, we comment on a recently discovered SRC-3 small molecular inhibitor.

Most targeted chemotherapeutic drugs block only a single cellular pathway. In response, cancers frequently acquire resistance by upregulating alternative pathways. SRC-3 coordinates multiple signaling networks, suggesting SRC-3 inhibition offers a promising therapeutic strategy. Development of an effective SRC-3 inhibitor faces critical challenges. Better understanding of SRC-3 function and interacting partners, in both the nucleus and cytosol, is required for optimized inhibitor development. Ultimately, blockade of SRC-3 oncogenic function may inhibit multiple cancer-related signaling pathways.