Nuclear Mechanisms Involved in Endocrine Resistance

Endocrine therapy is a standard treatment offered to patients with ER alpha (estrogen receptor alpha)-positive breast cancer. In endocrine therapy, ER alpha is either directly targeted by anti-estrogens or indirectly by aromatase inhibitors which cause estrogen deficiency. Resistance to these drugs (endocrine resistance) compromises the efficiency of this treatment and requires additional measures. Endocrine resistance is often caused by deregulation of the PI3K/AKT/mTOR pathway and/or cyclin-dependent kinase 4 and 6 activities allowing inhibitors of these factors to be used clinically to counteract endocrine resistance. The nuclear mechanisms involved in endocrine resistance are beginning to emerge. Exploring these mechanisms may reveal additional druggable targets, which could help to further improve patients' outcome in an endocrine resistance setting. This review intends to summarize our current knowledge on the nuclear mechanisms linked to endocrine resistance.

Automated summary

Endocrine therapy is a standard treatment for ER alpha-positive breast cancer, but resistance to these drugs can occur due to deregulation of certain pathways. Inhibitors targeting these pathways may help counteract endocrine resistance and improve patient outcomes. Further exploration of nuclear mechanisms involved in endocrine resistance could lead to the identification of additional druggable targets.