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Fig. 1 | BMC Medicine

Fig. 1

From: Targeted therapies for ER+/HER2- metastatic breast cancer

Fig. 1

Cross-talk between ER signaling and growth factor signaling pathways described as linked to resistance to endocrine therapy. Classical ER signaling needs to bind to estrogens and HSP90 chaperone protein before binding to transcription start site of target genes such as cyclin D. This transcription activity is partly mediated by histone deacetylation by HDAC6. CyclinD activates E2F transcription via Rb phosphorylation and promotes G1-S transition into the cell cycle for cell proliferation. Suppression of classical ER signaling by endocrine therapy might promote activation of the tyrosine kinase receptor signaling pathways PI3K/Akt/mTOR and RAS-RAF-MAPK via its effectors S6K1 and 4EBP1 to promote ligand-independent activation of ER. Numbers shown in this figure correspond to the function sites of the target agents described in the manuscript. mTOR inhibitor: inhibition of mTORC1 down-regulated S6K1 and 4EBP1. In mTOR inhibitor resistance, feedback signaling seems to be activated indicated by white arrow. , PI3K inhibitors and Akt inhibitors. CDK4/6 inhibitors. FGFR inhibitors. HDAC6 inhibitors. Specific inhibitory agents for mutant ER (ex. HSP90 inhibitors). This figure was exclusively drawn for this article

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