# Oestrogen receptor signalling

Source: https://onco.cc/pathways/er-signaling/  
OnCo record `er-signaling` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-04
- Analogy: 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.
- Interventions: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Estrogen_receptor
- Wikipedia: https://en.wikipedia.org/wiki/Estrogen_receptor

## Connected records

- cancers: [Ductal carcinoma in situ (DCIS)](https://onco.cc/cancers/ductal-carcinoma-in-situ/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Male breast cancer](https://onco.cc/cancers/male-breast-cancer/), [Uterine sarcoma](https://onco.cc/cancers/uterine-sarcoma/)
- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/), [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/)
- targets: [CDK4/6](https://onco.cc/targets/cdk4-6/), [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/), [FOXA1](https://onco.cc/targets/foxa1/), [MYC](https://onco.cc/targets/myc-gene/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/)
- drugs: [Abemaciclib](https://onco.cc/drugs/abemaciclib/), [Elacestrant](https://onco.cc/drugs/elacestrant/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Palbociclib](https://onco.cc/drugs/palbociclib/), [Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)](https://onco.cc/drugs/megestrol-progestins/), [Ribociclib](https://onco.cc/drugs/ribociclib/), [Vepdegestrant](https://onco.cc/drugs/vepdegestrant/)
- pairings: [CDK4/6 inhibitor + endocrine therapy](https://onco.cc/pairings/cdk46-plus-endocrine/), [PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)](https://onco.cc/pairings/pi3k-pathway-plus-endocrine/)
- pathways: [Breast cancer (KEGG map)](https://onco.cc/pathways/breast-cancer-signalling/), [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/), [Tumour dormancy](https://onco.cc/pathways/tumor-dormancy/)
- ideas: [Keep them asleep: dormancy maintenance as adjuvant therapy](https://onco.cc/ideas/idea-dormancy-maintenance-therapy/)
- terms: [Hormone therapy](https://onco.cc/terms/hormone-therapy/), [Signalling pathway](https://onco.cc/terms/signalling-pathway/)

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JSON: https://onco.cc/api/v1/entities/er-signaling.json