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Table 2 Mechanisms of endocrine resistance

From: The interaction between ER and NFκB in resistance to endocrine therapy

Influencing factor Mechanism Examples
Growth factors and kinases Influence on post-translational modifications of ER and its co-regulatory proteins, and influence on nongenomic ER activity EGFR/HER2, IGF1-R, FGFR, MAPK, PI3K
Cofactors Determine whether selective ER modulators act as agonist or antagonist and affect the ligand-independent activity of ER AIB1, NCOR1
Genes regulated by ER Interact with ERα and affect the level of hormone receptors and deregulate the cell cycle HSP90, FKBPL
Transcription factors Stimulate progression to estrogen independent tumor growth or modulate ER activity ERβ, AP1, NFκB
Genetic abnormalities Mutations in cytochrome p450 prevent tamoxifen to be converted to its active metabolite endoxifen CYP450, ER
  1. AIB1, amplified in breast 1; AP1, activator protein 1; CYP450, cytochrome p450; EGFR, epidermal growth factor receptor; ER, estrogen receptor; FGFR, fibroblast growth factor receptor; FKBPL, FK506-binding protein like; HSP90, heat shock protein 90; IGF1-R, insulin-like growth factor-1 receptor; MAPK, mitogen-activated protein kinase; NCOR1, co-repressor of estrogen receptor; PI3K, phosphatidylinositol-3 kinase.