Oestrogen receptor signalling
In hormone-positive breast cancer, oestrogen binds its receptor, which switches on genes that make the cell divide. Every endocrine therapy cuts this chain somewhere.
Aromatase converts androgens to oestradiol (in ovaries pre-menopause, fat and tumour post-menopause). Oestradiol binds ERα (ESR1), which dimerises, recruits co-activators, and drives transcription of cyclin D1, MYC, PGR, and growth factors, activating CDK4/6 and cross-talking with PI3K and HER2. Tamoxifen (SERM) competes; aromatase inhibitors deplete ligand; fulvestrant and oral SERDs degrade ER; vepdegestrant (PROTAC) degrades it via cereblon. Resistance: ESR1 ligand-binding-domain mutations (ligand-independent, ~30% after AI), cyclin D1/CDK4 amplification, PI3K activation, lineage switch.
In one picture
A key (oestrogen) turns a lock (ER) that opens a gate to the division machinery. Aromatase inhibitors stop making keys, tamoxifen jams a fake key in the lock, SERDs and PROTACs remove the lock from the door, and ESR1 mutations are a lock that opens without any key.
Diagram
top- Aromatase inhibitors (letrozole, anastrozole, exemestane) ± ovarian suppression
- SERMs (tamoxifen)
- SERDs: fulvestrant, elacestrant, imlunestrant, camizestrant
- PROTAC degrader vepdegestrant (2026)
- CDK4/6 inhibitors downstream; PI3K/AKT inhibitors for cross-talk
Pages like this
not linked directly; found by shared links- TrialMONALEESA-2
Shares Letrozole (and other aromatase inhibitors), Ribociclib, CDK4/6, Estrogen receptor (ERα).
- IdeaCDK4-selective inhibitors as the new first-line backbone
Shares Ribociclib, Abemaciclib, Palbociclib, CDK4/6.
- TrialPALOMA-2
Shares Letrozole (and other aromatase inhibitors), Palbociclib, CDK4/6, HR-positive / HER2-negative breast cancer.
- TermCell cycle
Shares Ribociclib, Abemaciclib, Palbociclib, CDK4/6 inhibitors.
- PersonSeock-Ah Im
Shares Ribociclib, Palbociclib, CDK4/6, Estrogen receptor (ERα).
- TrialMONARCH 3
Shares Letrozole (and other aromatase inhibitors), Abemaciclib, CDK4/6, HR-positive / HER2-negative breast cancer.
- TermEndocrine resistance
Shares The cell-cycle engine (cyclins & CDKs), PIK3CA / PI3K-alpha, CDK4/6, Estrogen receptor (ERα).
- TermESR1 mutation
Shares Vepdegestrant, Elacestrant, Transcriptional machinery & addiction, Estrogen receptor (ERα).