Figure 1.

Schematic representation of the cyclinD/CDK4/6 involvement in overpassing resistance to aromatase inhibitors. Aromatase converts androgens (A) in estrogens (E) that bind to ER receptor. The recruitment of co-activators (co-A) allows the binding to ERE element on the target genes and the activation of the transcription. AIs block the production of estrogen inhibiting the ER-driven activation of cell cycle progression. The activation of cyclinD/CDK4/6 complex, mediated by the protein kinase signaling pathway (PI3K/AKT/mTOR), stimulates cell proliferation independently from aromatase. The use of CDK4/6 inhibitor blocks this alternative activation pathway.