Regulation of hormonal therapy resistance by cell cycle machinery.

Estrogen Receptor (ER) plays a central role in the development and progression of breast cancer. Hormonal therapy substantially improves disease-free survival of ER+ve breast tumors, however acquired resistance to endocrine therapies frequently occur. Emerging data implicate growth factor signaling pathways and their cross talk with ER as major cause of resistance. Both these pathways have been recently shown to use cell cycle machinery as downstream effectors in mediating therapy resistance. Several studies have demonstrated deregulation of cell cycle regulators and their cross talk with ER in therapy resistant tumors. The objective of this article is to review the underlying mechanisms by which tumor cells use cell cycle machinery to override hormonal therapy and to explore cell cycle machinery components as novel therapy targets for overcoming hormonal therapy resistance.