**8. Discussion and conclusion**

AIB1 in an oncogene that contributes to disease progression in multiple cancers. It primarily acts to augment transcriptional activity, thereby amplifying proproliferative and pro-tumorigenic signaling cascades through binding to its many partners. Though primarily studied for its role in interacting with nuclear hormone receptors, AIB1 has been clearly implicated to play an oncogenic role in hormone independent cancers. Genetic manipulation or removal of the NCOA3 gene has almost universally slowed cancer progression wherever studied, likely by dampening all of the pathways it usually effects. From this role, its clinical importance is obvious, as its elevated levels is usually a negative prognostic marker.

Most clinical studies have underscored the importance of AIB1 in the progression of human disease. Overwhelmingly, expression of AIB1 is correlated with poor prognosis in breast, ovarian, pancreatic, prostate, and colon cancer, as well as increased metastasis [25, 100]. Heightened AIB1 levels have successfully been used in the clinic as a negative prognostic marker in post-menopausal breast cancer [101] and may mark tamoxifen resistance [102]. Further, preclinical investigation of compounds that promote the degradation of AIB1 have shown promising results in attenuating the effects of the oncogene [103, 104]. Interestingly, pharmacological hyperstimulation of AIB1 has also been shown to induce cell death by increasing cell stress [105].

Clarifying the extent to which AIB1 is critical in bridging cooperating transcription factors will further explain intracellular signaling biology and may also provide new targets for therapeutic development. Also, there remains a gap in knowledge surrounding the role of the AIB1Δ4 in the nucleus, especially in regard to global binding and transcriptional patterns of the isoform. Finally, elucidating the importance of AIB1 as an effector of growth factor and cytokine signaling may explain its potent oncogenic nature. It is clear that AIB1 may be both a clinically relevant prognostic marker and a promising therapeutic target, as evidenced by the promising preclinical data.
