Estrogen receptor-positive breast cancer signaling network (ER+ BC signaling)

Estrogen receptor-positive (ER+) breast cancer signaling networks encompass a diverse array of molecular targets and pathways that drive the growth and survival of the most common subtype of breast cancer. At the core of this network is the Estrogen receptor alpha (ERα), a nuclear receptor that acts as a ligand-activated transcription factor to regulate genes involved in cell cycle progression and survival (UniProt P03372). Beyond direct ER signaling, these networks involve extensive cross-talk with growth factor pathways, such as the PI3K/AKT/mTOR and MAPK/ERK cascades, which often provide bypass mechanisms for cell growth (PMID: 30135553). The Cyclin D-CDK4/6-Rb axis is another critical component, serving as a downstream integrator of these signals to control the G1-S phase transition of the cell cycle. Therapeutic strategies targeting this network include endocrine therapies like selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (StatPearls: NBK538209). To address resistance, these are frequently combined with targeted inhibitors of CDK4/6, PI3K, or mTOR (NCI). Monitoring biomarkers such as ESR1 and PIK3CA mutations is essential for managing the evolving landscape of these signaling networks during treatment. Overall, the integration of these pathways determines the clinical phenotype and therapeutic response in ER+ breast cancer patients.

Other names

ER-positive breast cancer targetsEstrogen receptor signaling pathwayER+ breast cancer signaling axisER-positive breast cancer–related targets and signaling networks

Inhibition of estrogen receptor activity through competitive antagonism or degradation, suppression of estrogen synthesis, and targeted inhibition of auxiliary signaling kinases like CDK4/6 and PI3K.